Neoplasma[JOURNAL]
Sun
200 papers
Integrated transcriptomic and proteomic analysis reveals the mechanistic role of OST in cutaneous squamous cell carcinoma.
Wang Y, Ding H, Gao T … +4 more , Ji B, Gao Y, Yan W, Wang J
Neoplasma · 2025 Dec · PMID 41567021 · Publisher ↗
Osthole (OST) is a natural component of the traditional Chinese medicinal herb, Cnidium monnieri, that exhibits antipruritic properties and may exert effects on dermatitis. Numerous previous studies have focused on the e...
Osthole (OST) is a natural component of the traditional Chinese medicinal herb, Cnidium monnieri, that exhibits antipruritic properties and may exert effects on dermatitis. Numerous previous studies have focused on the effects of OST in tumors; however, the potential impact on cutaneous squamous cell carcinoma (CSCC) remains to be fully elucidated. Thus, the present study aimed to evaluate CSCC cell proliferation following treatment with OST, and further analyzed the underlying mechanisms using multi-omics analyses. Due to their cancerous characteristics, both A431 and SCL-1 cells are used in drug screening and testing for CSCC, particularly for therapies targeting growth pathways and markers associated with SCC. Results of the flow cytometry analysis demonstrated that OST impacted the CSCC cell cycle, causing arrest in the G2 phase. Notably, OST exerted a slight growth-promoting effect on healthy skin HaCaT cells. In addition, our omics results revealed that there were 1,720 differentially expressed genes and 227 differentially expressed proteins in the OST-treated group. Transcriptomics combined with proteomics analyses revealed that 5 of the top 20 screened pathways were associated with the cell cycle, and ATR, CENPJ, and RAD54B were highlighted as specific targets for OST-mediated regulation. Collectively, these results suggested that OST has a potential inhibition on human CSCC cells, and ATR, CENPJ, and RAD54B may be the key factors regulated by OST in A431's cell cycle progression inhibition.
LINC00324 suppresses abnormal proliferation and promotes apoptosis of leukemia cells through the miR-10b-5p/PTEN pathway.
Li Y, Wang B, Lin F … +8 more , Zhang Y, Lan Y, Liu Y, Bao W, Xie B, Zhou Q, Zhou J, Zeng Q
Neoplasma · 2025 Dec · PMID 41567020 · Publisher ↗
Long non-coding RNAs (lncRNAs) are known to participate in leukemia development, but the molecular mechanisms of many remain unclear. The expression of LINC00324 was examined in peripheral blood samples from leukemia pat...
Long non-coding RNAs (lncRNAs) are known to participate in leukemia development, but the molecular mechanisms of many remain unclear. The expression of LINC00324 was examined in peripheral blood samples from leukemia patients and in leukemia cell lines by RT-qPCR. Functional studies were performed to evaluate how LINC00324 overexpression or knockdown affected cell proliferation and apoptosis. Flow cytometry was used to detect apoptosis. Western blotting was applied to measure Ki-67, BAX, Bcl-2, and PTEN protein levels. Dual-luciferase reporter assays were used to confirm the interaction among LINC00324, miR-10b-5p, and PTEN. LINC00324 expression was markedly reduced in leukemia samples and cell lines. Upregulation of LINC00324 inhibited the proliferation of Jurkat and HL-60 cells and increased apoptosis, while its silencing produced the opposite trend. Western blotting showed that LINC00324 overexpression decreased Ki-67 and Bcl-2 but increased BAX expression. Rescue experiments demonstrated that miR-10b-5p mimics reversed, whereas inhibitors restored, the effects of LINC00324. Bioinformatics prediction and luciferase validation identified PTEN as a direct target of miR-10b-5p, and LINC00324 enhanced PTEN expression by sponging miR-10b-5p. LINC00324 regulates the proliferation and apoptosis of leukemia cells through the miR-10b-5p/PTEN axis. These findings add to the understanding of lncRNA-mediated regulatory mechanisms in leukemia.
HERC1 attenuates gemcitabine resistance of lung cancer cells by inhibiting autophagy through KAT2A ubiquitination.
Wei Y, Tian G, Tang Z … +3 more , Ding S, Tang Z, Luo P
Neoplasma · 2025 Dec · PMID 41567019 · Publisher ↗
Lung cancer, a leading cause of death, is challenging to treat due to gemcitabine resistance. Dysregulated autophagy is associated with chemoresistance. Here, we aimed to study the mechanism of how HERC1 modulates autoph...
Lung cancer, a leading cause of death, is challenging to treat due to gemcitabine resistance. Dysregulated autophagy is associated with chemoresistance. Here, we aimed to study the mechanism of how HERC1 modulates autophagy and gemcitabine sensitivity in lung cancer. Paired tumor and adjacent normal tissues were collected from 30 patients with lung cancer. The viability, proliferation, apoptosis, migratory, and invasive capacity of gemcitabine-resistant A549 and H1299 cells (A549/R and H1299/R) were evaluated using Cell Counting Kit-8 (CCK-8), EdU staining, flow cytometry, wound healing, and Transwell assays, respectively. The interactions among HECT and RLD domain-containing E3 ubiquitin protein ligase family member 1 (HERC1)-lysine acetyltransferase 2A (KAT2A)-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) were verified by co-immunoprecipitation. A mouse xenograft tumor model was established. Ki-67 expression was determined by immunohistochemistry. Our data showed that HERC1 expression was downregulated in gemcitabine-resistant tumor tissues and A549/R cells, correlating with poor prognosis. Overexpressing HERC1 suppressed proliferation and migration, enhanced apoptosis in A549/R or H1299/R cells, and simultaneously inhibited autophagy. Mechanistically, HERC1 promoted KAT2A ubiquitination and degradation, which enhanced gemcitabine sensitivity by inhibiting autophagy. Further investigation revealed that KAT2A depletion inhibited the lysine acetylation modification of PIK3CB, leading to inactivation of the PI3K/AKT axis. Additionally, HERC1 suppressed autophagy and gemcitabine resistance in A549/R cells by KAT2A-dependent inactivation of the PI3K/AKT axis. Furthermore, HERC1 overexpression enhanced the inhibition of gemcitabine on tumor growth by suppressing autophagy in vivo. In conclusion, HERC1 inhibited autophagy by inactivating PIK3CB-mediated PI3K/AKT signaling via promoting KAT2A degradation, thereby enhancing the gemcitabine sensitivity in lung cancer.
Stem cells-derived suicide gene exosomes: a promising platform for innovative cancer therapy.
Vanova D, Andrezal M, Altanerova U … +2 more , Matuskova M, Altaner C
Neoplasma · 2026 Feb · PMID 41410507 · Publisher ↗
Innovative cancer treatments are needed for metastatic tumors that currently do not have adequate therapies. This review highlights recent progress in suicide gene therapy using small extracellular vesicles, particularly...
Innovative cancer treatments are needed for metastatic tumors that currently do not have adequate therapies. This review highlights recent progress in suicide gene therapy using small extracellular vesicles, particularly exosomes, as a novel form of intracellular anticancer therapy. Suicide gene exosomes are produced by tumor-targeting human mesenchymal stem cells (MSC) that have been genetically modified to express the yeast cytosine deaminase::uracil phosphoribosyl transferase fused gene (yCD::UPRT) along with the prodrug 5-fluorocytosine (5-FC). The yCD::UPRT-MSC-secretome containing tumor-targeted exosomes converts 5-FC into the cytotoxic compound 5-fluorouracil (5-FU) and its metabolites within the tumor environment. The second popular system we are investigating involves the suicide gene exosomes derived from thymidine kinase of Herpes Simplex Virus in conjunction with a prodrug ganciclovir. Extracellular vesicles secreted by tumor-associated cells contribute to tumor growth and metastasis. When these cells are transduced with yCD::UPRT suicide gene, they can act as a source of therapeutic exosomes capable of intracellularly converting nontoxic prodrug 5-FC to a cytotoxic 5-FU. Combined action of suicide gene exosomes from MSCs and cancer-associated fibroblasts is a promising platform for aggressive tumor treatment. Furthermore, suicide gene exosomes can be enhanced with additional anticancer drugs and customized for targeted delivery. In this review, we trace the history of these findings, present therapeutic outcomes from in vitro and in vivo studies, and explore the future potential of therapeutically beneficial exosomes for cancer treatment.
Immune checkpoint remodeling across disease progression in multiple myeloma.
Valuskova Z, Cholujova D, Beke G … +5 more , Hucko M, Klucar L, Grofova G, Drgona L, Jakubíková J
Neoplasma · 2026 Feb · PMID 41410506 · Publisher ↗
Immune checkpoint dynamics within the bone marrow (BM) critically shape disease evolution and therapeutic responses in multiple myeloma (MM). To delineate immune remodeling in the BM during plasma cell malignancy evoluti...
Immune checkpoint dynamics within the bone marrow (BM) critically shape disease evolution and therapeutic responses in multiple myeloma (MM). To delineate immune remodeling in the BM during plasma cell malignancy evolution, we profiled inhibitory (PD-1, CTLA-4, LAG-3, TIM-3, TIGIT, BTLA, and 2B4) and co-stimulatory (ICOS, CD27, DNAM-1, 4-1BB, and OX40) checkpoints across adaptive and select innate compartments in healthy donors (HD, n=25), monoclonal gammopathy of undetermined significance (MGUS, n=17), newly diagnosed MM (NDMM, n=57), and relapsed/relapsed-refractory MM (MM, n=72; on-treatment n=27, off-treatment n=12). Progressive disease featured loss of mature, memory, and activated/proliferating B cell subsets and an NDMM-specific expansion of plasmablasts/plasma cells. B cell maturation was accompanied by broad remodeling of inhibitory receptors (notably reduced PD-1, TIM-3, TIGIT, and 2B4 on mature B cells; decreased CTLA-4 on activated B cells and plasmablasts/plasma cells; and reduced TIM-3, LAG-3, and 2B4 on plasmablasts/plasma cells) alongside selective co-stimulatory changes (OX40 decreased on mature B cells; CD27 loss on activated and plasmablast/plasma compartments; divergent 4-1BB regulation). T cell compartments showed early CD4+ expansion with CD8+ cytotoxic reduction and checkpoint shifts: broad PD-1 downregulation with subset-restricted increases in LAG-3, TIM-3, TIGIT, and BTLA; variable upregulation of CD27, DNAM-1, and ICOS; and consistent 4-1BB loss. NKT and γδ T cell frequencies were stable, but their checkpoints were reconfigured: NKT cells exhibited decreased PD-1 and 4-1BB and increased TIGIT, LAG-3, and DNAM-1, whereas γδ T cells showed reduced CTLA-4, BTLA, and the co-stimulatory receptor OX40. Innate NK cells demonstrated reduced frequency and phenotypic shifts, including decreased TIM-3 and PD-1, loss of 4-1BB and OX40, stage-specific increases in TIGIT and 2B4, and elevated DNAM-1. Checkpoint alterations, such as low TIGIT or CTLA-4 and elevated OX40 expression, were correlated with superior progression-free survival. MM progression entails extensive, stage- and subset-specific remodeling of inhibitory and activating immune checkpoints in the BM, with implications for immunotherapeutic targeting.
Bystin-like protein forms a functional complex with DDX49 to enhance thyroid cancer progression.
Wang Y, Xing X, Zhang D … +5 more , Sun T, Zhang Y, Li J, Liao D, Li J
Neoplasma · 2026 Feb · PMID 41410505 · Publisher ↗
The incidence of thyroid cancer is rising worldwide, underscoring the urgent need for novel molecular targets in the management of aggressive disease. This study identifies bystin-like protein (BYSL) as a previously unre...
The incidence of thyroid cancer is rising worldwide, underscoring the urgent need for novel molecular targets in the management of aggressive disease. This study identifies bystin-like protein (BYSL) as a previously unrecognized oncogenic driver in thyroid carcinoma. Comprehensive analyses of clinical specimens, established cell lines, and patient-derived tumor-like clusters revealed that BYSL is significantly upregulated in thyroid malignancies and is strongly correlated with adverse patient outcomes. Functional assays demonstrated that BYSL promotes tumor cell proliferation, migration, and invasion while suppressing apoptosis. Mechanistically, BYSL interacts directly with DEAD-box helicase 49 (DDX49) to form a functional protein complex that impairs the biogenesis of the tumor suppressor miR-145-5p by inhibiting its DICER-mediated processing. Dual knockdown of BYSL and DDX49 synergistically suppressed tumor growth and induced apoptosis in patient-derived tumor-like cell clusters, with these effects reversed by inhibition of miR-145-5p. Collectively, these findings demonstrate the BYSL-DDX49 complex as a pivotal modulator of thyroid cancer progression and underscore its promise as a therapeutic intervention for restoring tumor-suppressive pathways.
Peroxisome proliferator-activated receptors as novel targets of small cell lung cancer circulating tumor cells.
Hamilton G, Eggerstorfer MT, Weigl L … +2 more , Hochmair MJ, Stickler S
Neoplasma · 2025 Dec · PMID 41288066 · Publisher ↗
Small cell lung cancer (SCLC) has a dismal prognosis with a low 2-year survival rate. Chemotherapy for recurrent SCLC fails invariably, and novel tumor targets are needed. Here, the effects of agents targeting the peroxi...
Small cell lung cancer (SCLC) has a dismal prognosis with a low 2-year survival rate. Chemotherapy for recurrent SCLC fails invariably, and novel tumor targets are needed. Here, the effects of agents targeting the peroxisome proliferator-activated receptors (PPARs) in SCLC are investigated. Initial screening of 96 PPAR-directed agents was performed in two SCLC CTC-derived lines (BHGc10, BHGc16). Compounds showing high cytotoxicity were subsequently tested in two pleural effusion-derived lines (S457, S1392) and the SCLC line NCI-H69. Several PPARs emerged as actionable targets: eight PPARγ ligands and nine ligands for PPARα, PPARα/δ, or PPARβ/δ. For the six most effective compounds, treatment-induced protein changes were further profiled in BHGc16 using protein arrays. Cytotoxicity varied by compound, while the PPARγ agonist pioglitazone and the PPARα agonist fenofibrate were preferentially active in CTC lines, DG172 hydrochloride was selective for pleural effusion-derived lines, while rosiglitazone maleate, cloxiquine, and agrimol B showed no selectivity. Mechanistically, in the CTC-derived cell line BHGc16, these six PPAR-directed agents increased pro-apoptotic proteins (Bax, Bad, caspase-3/9), decreased anti-apoptotic and invasion proteins (Bcl-2, Bcl-XL, c-FLIP-L, ICAM-1, CXCR4), and suppressed Akt/mTOR, MEK/ERK, p38 MAPK, and JAK2/STAT3 signaling. These findings support PPARs as clinically relevant targets in SCLC, with PPAR-directed agents showing cytotoxic effects comparable to those reported in other malignancies. Such agents may aid SCLC treatment and help delineate biological differences between CTCs and resident tumor cells.
Efficacy and safety of adebrelimab plus bevacizumab in combination with hepatic artery infusion chemotherapy for advanced stage hepatocellular carcinoma: a retrospective cohort study.
Li C, Lin L, Chen S … +9 more , Nuerhashi G, Tan H, Wen C, Wang Y, Zheng G, Tang R, Pan J, Shen L, Fan W
Neoplasma · 2026 Feb · PMID 41288065 · Publisher ↗
Hepatic arterial infusion chemotherapy using a combination of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) has shown promise for patients with advanced-stage hepatocellular carcinoma (HCC). In this study, we a...
Hepatic arterial infusion chemotherapy using a combination of oxaliplatin, fluorouracil, and leucovorin (HAIC-FOLFOX) has shown promise for patients with advanced-stage hepatocellular carcinoma (HCC). In this study, we aim to evaluate the efficacy and safety of combining adebrelimab (anti-PD-L1 antibody) and bevacizumab with HAIC-FOLFOX for HCC patients in BCLC stage C. This retrospective study included 32 untreated advanced-stage HCC patients receiving HAIC-FOLFOX combined with adebrelimab and bevacizumab as first-line therapy. The primary endpoint is overall response rate (ORR) based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. From January 14th, 2024, to December 5th, 2024, a total of 32 patients received the triplet combination of HAIC-FOLFOX, adebrelimab, and bevacizumab. Median follow-up time was 6.1 months. According to RECIST v1.1 criteria, the confirmed ORR was 71.8% (95% CI: 55.4-88.3%), with a disease control rate (DCR) of 93.7% (95% CI: 84.9-99.9%). Only one case (3.1%) had a grade 3 treatment-related adverse event (rash), which could be alleviated after symptomatic management. The combination of adebrelimab, bevacizumab, and HAIC-FOLFOX demonstrated encouraging results and manageable safety concerns for patients with HCC at BCLC stage C.
The infratentorial localization of brain metastases in non-small cell lung cancer indicates poorer prognosis and a distinct selection of radiotherapy.
Liu Z, Chen Z, Lu F … +5 more , Tan S, Peng N, Shang C, Wu S, Xia Y
Neoplasma · 2025 Dec · PMID 41288064 · Publisher ↗
Infratentorial brain metastases (BMs) are life-threatening because of the unique anatomical features and physiological functions of the posterior cranial fossa. However, the comparative prognosis of infratentorial BM and...
Infratentorial brain metastases (BMs) are life-threatening because of the unique anatomical features and physiological functions of the posterior cranial fossa. However, the comparative prognosis of infratentorial BM and supratentorial BM remains poorly understood. We conducted a matching comparison of the prognosis between non-small cell lung cancer (NSCLC) patients with and without infratentorial BM and analyzed prognostic factors, including the radiotherapy (RT) method. 392 NSCLC patients who underwent brain RT from July 2010 until June 2023 were analyzed. After 1:1 propensity matching, we compared 115 patients with only supratentorial BMs (supraT-alone group) and 115 patients with infratentorial ± supratentorial BMs (infraT ± supraT group). We assessed intracranial control and overall survival (OS) using Kaplan-Meier and Cox regression. There was no statistical difference for extracranial progression-free survival (PFS), intracranial local PFS, or distant PFS. The supraT-alone group had significantly better OS (median: 35.3 vs. 24.2 months, p=0.021). The supraT-alone group in the multivariate analysis had BM resection (p=0.031), targeted therapy (p<0.001), and immune therapy (p=0.006) associated with improved OS. The infraT ± supraT group had RT method (p=0.002), ≤60 years of age (p=0.002), targeted therapy (p=0.017), and number of extracranial metastases (p<0.001) when reporting OS. We confirmed that WBRT+boost and SRT improved OS compared to WBRT alone. There was no statistical difference in OS for WBRT+boost and SRT. The overall grade 3-4 acute toxicities were similar for both groups. Our study suggests that infratentorial BMs in NSCLC lead to worse OS. However, local high-dose RT strategies (SRT or WBRT+boost) may confer survival benefits to patients who present with infratentorial involvement.
Corrigendum: EGLN2 attenuates ovarian cancer malignancy via ferroptosis activation.
Wu Y, Chen H, Jiang S … +3 more , Wu X, Li D, Xie K
Neoplasma · 2025 Oct · PMID 41235532 · Publisher ↗
This corrects the article DOI:10.4149/neo_2025_250411N162.
This corrects the article DOI:10.4149/neo_2025_250411N162.
WDR4 promotes glioma progression by regulating cell proliferation and cell cycle via the PI3K/Akt-CDK1/2 signaling pathway.
Liu J, Zhang Z, Xue S … +10 more , Huang G, Yuan J, Cai Y, Zhan Z, Liu G, Zhang B, Ye X, Song Y, Li P, Guo H
Neoplasma · 2025 Oct · PMID 41235531 · Publisher ↗
WD Repeat Domain 4 (WDR4) is integral to the development and progression of various cancers; however, its specific role and underlying molecular mechanisms in glioma remain inadequately elucidated. This study undertook a...
WD Repeat Domain 4 (WDR4) is integral to the development and progression of various cancers; however, its specific role and underlying molecular mechanisms in glioma remain inadequately elucidated. This study undertook an analysis of WDR4 expression levels in glioma and normal brain tissues utilizing publicly accessible datasets from TCGA and GTEx project, with further validation conducted through the GEPIA and the HPA databases. Prognostic significance was assessed using Kaplan-Meier survival analysis and multivariate Cox regression models. Cellular functions were investigated through CCK-8 viability assays, colony formation assays, and cell cycle analysis, while the tumorigenic potential in vivo was corroborated using a nude mouse xenograft model. The findings revealed a significant upregulation of WDR4 in both glioma tissues and cell lines. Elevated WDR4 expression correlated with reduced overall survival and emerged as an independent prognostic factor. Functional assays indicated that WDR4 silencing markedly inhibited glioma cell proliferation, induced G1 phase cell cycle arrest, and resulted in the downregulation of CDK1 and CDK2 protein expression. Further co-expression analysis, GSEA, KEGG pathway enrichment, and western blotting suggested that WDR4 may exert its oncogenic effects through activation of the PI3K/Akt signaling pathway. In conclusion, WDR4 is highly expressed in glioma and promotes tumor progression via the PI3K/Akt-CDK1/2 signaling axis. These findings indicate that WDR4 may serve as a potential prognostic biomarker and therapeutic target in glioma.
Upregulation of SIRT6 enhances autophagy-dependent ferroptosis of colorectal cancer cells through inactivating the mTOR/STAT3 signaling pathway.
Wang Y, Xu H, Shen Y … +2 more , Liu L, Liu X
Neoplasma · 2025 Oct · PMID 41235530 · Publisher ↗
Accumulating evidence highlights the critical roles of autophagy-dependent ferroptosis mediators in colorectal cancer (CRC) pathogenesis. To elucidate SIRT6's tumor-suppressive role, HT29 cells stably overexpressing SIRT...
Accumulating evidence highlights the critical roles of autophagy-dependent ferroptosis mediators in colorectal cancer (CRC) pathogenesis. To elucidate SIRT6's tumor-suppressive role, HT29 cells stably overexpressing SIRT6 (Oe-SIRT6) were generated via plasmid transfection. Functional assays were performed to evaluate autophagy and ferroptosis. Rescue experiments using the autophagy inhibitor 3-MA or the mTOR agonist MHY1485 were conducted. Quantitative analyses revealed marked downregulation of SIRT6 expression in CRC cell lines (SW620, SW480, and HT29) compared to normal colon epithelial cells. SIRT6 overexpression induced autophagy and activated ferroptosis. The autophagy inhibitor 3-MA blocked SIRT6-driven ferroptosis, which confirmed its dependency on autophagy. Moreover, SIRT6 was found to inactivate mTOR/STAT3 signaling, whereas the mTOR agonist MHY1485 reversed SIRT6 overexpression on autophagy-dependent ferroptosis of CRC cells. Our findings establish SIRT6 as a dual-phase regulator of CRC cell death, suppressing mTOR/STAT3 signaling to orchestrate autophagy-dependent ferroptosis.
Lymphopenia in glioblastoma and its association with brain vessel irradiation: pilot retrospective evaluation of dose-volume parameters.
Hnidakova L, Selingerova I, Pospisil P … +11 more , Halamkova J, Belanova R, Nikl T, Sana J, Vavrusakova B, Bartosova R, Slaby O, Slampa P, Jancalek R, Minniti G, Kazda T
Neoplasma · 2025 Oct · PMID 41235529 · Publisher ↗
Radiotherapy (RT) plays a central role in the management of glioblastoma, often in combination with other treatment modalities. While RT can enhance both local and systemic tumor control, especially when used alongside i...
Radiotherapy (RT) plays a central role in the management of glioblastoma, often in combination with other treatment modalities. While RT can enhance both local and systemic tumor control, especially when used alongside immunotherapy, it is also associated with lymphopenia - a reduction in lymphocyte count - which has been linked to poorer treatment outcomes and reduced survival. This retrospective study aimed to examine the relationship between radiation dose delivered to brain vessels and the severity of lymphopenia in patients with newly diagnosed glioblastoma treated at a tertiary cancer center in 2021. Brain vessels were manually contoured using MRI data, and dose-volume analysis was conducted. Lymphopenia severity was graded according to CTCAE v5.0, and statistical analyses were performed to identify any correlations. Among the 28 patients analyzed, 32% developed grade 1-3 lymphopenia. No significant correlation was found between the radiation dose to brain vessels and the degree of lymphopenia. The median volume of irradiated vessels did not differ significantly between patients with and without lymphopenia. In glioblastoma patients, multiple factors contribute to decreased lymphocyte count - e.g., chemotherapy and corticosteroid use. Although no definitive link was identified, the study underscores the importance of preserving lymphocyte counts during glioblastoma treatment and supports the need for further prospective research to explore strategies like lymphocyte-sparing RT and to better understand the mechanisms behind treatment-related lymphopenia.
Establishment of a metastatic patient-derived xenograft model of breast carcinoma.
Bohac M, Cumova A, Cihova M … +9 more , Trnkova L, Sedlackova E, Tran MT, Novotna N, Karaba M, Dyttert D, Durdik S, Mego M, Burikova M
Neoplasma · 2025 Oct · PMID 41235528 · Publisher ↗
In this study, we investigated the development and application of patient-derived xenograft (PDX) models for metastatic breast carcinoma. Orthotopic PDX models were established from tumor tissue of invasive ductal breast...
In this study, we investigated the development and application of patient-derived xenograft (PDX) models for metastatic breast carcinoma. Orthotopic PDX models were established from tumor tissue of invasive ductal breast carcinoma patients without prior neoadjuvant therapy. Following successful tumor engraftment in immunodeficient NOD SCID gamma (NSG) mice, primary tumors were surgically excised using a procedure simulating radical mastectomy, enabling extended post-operative survival for the development of eventual metastases. Tumor growth, the presence of lung metastases, along with their histopathological features and immunohistochemical profiles, were evaluated. Three stable and transplantable PDX models were successfully established. Spontaneous lung metastases developed in one model following surgical resection, and this metastatic capability was preserved across multiple in vivo passages. Despite the successful engraftment, significant discrepancies were observed between the immunohistochemical characteristics of the original patient tumors and their corresponding PDXs, particularly in hormone receptor status and Ki-67 proliferation marker expression. These findings highlight the challenges of maintaining molecular fidelity in traditional PDX models.
The mir-371a-373 cluster: A crucial miRNA cluster promotes the malignancy of gastric cancer.
Mao Z, Pan Y, Wu J … +8 more , Xiang A, Zhu K, Li J, Guo J, Tang N, Zhang J, Liu J, Rui T
Neoplasma · 2025 Oct · PMID 41017651 · Publisher ↗
Gastric cancer is one of the most common and deadliest malignancies worldwide. Better knowledge of the risk factors for gastric cancer is essential for risk classification and therapeutic strategy evolution in gastric ca...
Gastric cancer is one of the most common and deadliest malignancies worldwide. Better knowledge of the risk factors for gastric cancer is essential for risk classification and therapeutic strategy evolution in gastric cancer patients. Many kinds of miRNA clusters participate in tumorigenesis and tumor progression. Herein, we sought to screen and certify the crucial miRNA cluster for prognosis prediction and potential therapeutic targets in gastric cancer. The results showed that the mir-371a-373 cluster was the most highly expressed miRNA cluster in gastric cancer. The high expression of the mir-371a-373 cluster (mir-371a, mir-372, and mir-373) was positively associated with the poor overall survival of gastric cancer patients. The expression of mir-373 was correlated with early gastric cancer recurrence. mir-373 was an independent risk factor for gastric cancer recurrence and mortality. Then, gain- and loss-of-function experiments demonstrated that mir-373 could promote the malignancy of gastric cancer cells in vitro and in vivo. Through bioinformatics analysis and experimental validation, mir-373 was correlated with tumor regulation, and ZFP91 was the direct target of mir-373. Our findings suggest that the miR-371-373 cluster, especially mir-373, could be a robust marker for the prognosis prediction of gastric cancer and a potential therapeutic target for gastric cancer.
Overexpression of TNFα in colorectal cancer cell lines affects tumorigenicity, differentiation, and immune cell infiltration.
Tyciakova S, Makovicky P, Hricova V … +3 more , Rojikova L, Burikova M, Matuskova M
Neoplasma · 2025 Oct · PMID 41017650 · Publisher ↗
The progression of cancer strongly depends on the tumor microenvironment and immune surveillance. Tumor necrosis factor alpha (TNFα), a key inflammatory cytokine, can drive both tumor elimination and promotion, depending...
The progression of cancer strongly depends on the tumor microenvironment and immune surveillance. Tumor necrosis factor alpha (TNFα), a key inflammatory cytokine, can drive both tumor elimination and promotion, depending on its dose and the type of cancer. Colorectal cancer cell lines HCT 116, HT-29, and melanoma cells A375 engineered to stably overexpress the human TNFα gene were used to induce experimental subcutaneous tumors in two immunodeficient mouse strains: athymic Balb/c-nu/nu and SCID/bg mice. In athymic mice, TNFα-overexpressing cells completely lost their tumorigenicity. In SCID/bg mice, with no mature T and B cells and defective NK cells, the TNFα-overexpressing cells formed rudimentary flat ulcerous xenografts with rapidly reduced size, with tumor penetrance of 50-85%. Histopathological analysis revealed necrotic lesions, a more differentiated phenotype of tumor cells forming pseudoglandular structures, and more abundant stromal cells. Intratumoral infiltration of immune cells increased in TNFα-secreting tumors. Positivity of cytokeratins 7 and 20 in colorectal cancer xenografts was decreased. Paradoxically, the expression of ALDH1A1 and ALDH1A3 isoforms, which are important for disease prognosis, was increased. Our study suggests that careful modulation of the tumor microenvironment to a tumor-suppressive one using cytokine TNFα and controlled stimulation of antitumor immunity can contribute to the improvement of cancer treatment.
Salinomycin promotes cell death via the activation of the ROS/NF-κB/NLRP3 pathway in cholangiocarcinoma.
Zhou X, Yang F, Ling Y … +4 more , Huang L, Xing R, Lan Y, Zhang Y
Neoplasma · 2025 Oct · PMID 41017649 · Publisher ↗
Salinomycin (Sal), an ionophore antibiotic, has shown promising anti-cancer activity in multiple cancers. In this study, we aimed to investigate the effect of Sal on the ROS/NF-κB/NLRP3 pathway in cholangiocarcinoma (CCA...
Salinomycin (Sal), an ionophore antibiotic, has shown promising anti-cancer activity in multiple cancers. In this study, we aimed to investigate the effect of Sal on the ROS/NF-κB/NLRP3 pathway in cholangiocarcinoma (CCA) in vitro and in vivo. We observed that Sal inhibited cell proliferation, migration, and invasion. Sal promoted an increase of Annexin-V positive cells in Huh-28 and RBE cells in a dose-dependent manner, which was efficiently inhibited by VX-765 (Caspase-1 inhibitor), while Sal-induced increase of ROS levels was partially inhibited by exposure to N-acetyl-L-cysteine (ROS scavenger). Moreover, Sal inhibited tumor growth in RBE tumor-bearing mice. The activation of Sal on the ROS/NF-κB/NLRP3 pathway was also identified in CCA cells and tumor tissues. Collectively, these results suggested that Sal activated the ROS/NF-κB/NLRP3 pathway to promote pyroptosis-induced cell death in CCA and suggest it may be a promising treatment strategy for anti-CCA.
N6-methyladenosine-induced hsa_circ_0011536 acts as a microRNA-576-5p sponge to promote ferroptosis of non-small cell lung cancer cells via transferrin receptor.
Huang J, Deng C, Zhu H … +3 more , Chen X, Chen P, Du S
Neoplasma · 2025 Aug · PMID 40958523 · Publisher ↗
Lung cancer is the leading cause of death and the most diagnosed cancer worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; 85% of lung cancer patients are diagnosed with NSCLC. Though n...
Lung cancer is the leading cause of death and the most diagnosed cancer worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer; 85% of lung cancer patients are diagnosed with NSCLC. Though numerous treatments for lung cancer have been developed, the 5-year survival rate of patients with NSCLC remains low. Therefore, it is urgent to explore novel targets for NSCLC treatment. Growing evidence has revealed that circular RNAs (circRNAs) contribute to NSCLC progression. Besides, the data of circRNA microarray (GSE158695) has found that hsa_circ_0011536 is downregulated in NSCLC tissues. Nevertheless, the role of hsa_circ_0011536 in NSCLC remains unknown. In this study, RNA 6-methyladenosine (m6A) modification was detected by methylated RNA immunoprecipitation, the interaction of RNAs was determined using miRNA pulldown and luciferase reporter assay, while ferroptosis was identified by Cell Counting Kit-8 assay, intracellular iron content, and malondialdehyde level. Our findings demonstrated that hsa_circ_0011536 was downregulated in NSCLC cell lines. Mechanism investigation revealed that m6A modification enhanced the back-splicing of pre-ZMYM4 to increase hsa_circ_0011536 expression in A549 and NCI-H1299 cells. Moreover, hsa-miR-576-5p was the target of hsa_circ_0011536, while transferrin receptor (TFRC) was the downstream target of hsa-miR-576-5p in A549 and NCI-H1299 cells. Furthermore, hsa_circ_0011536 elevated TFRC expression by sponging hsa-miR-576-5p in A549 and NCI-H1299 cells, identified by luciferase reporter assay. In addition, hsa_circ_0011536 induced ferroptosis through hsa-miR-576-5p in A549 and NCI-H1299 cells. Therefore, this study revealed that m6A-induced hsa_circ_0011536 elevated TFRC expression to induce ferroptosis by sponging hsa-miR-576-5p in NSCLC. These results might provide novel therapeutic targets for NSCLC treatment.
EGLN2 attenuates ovarian cancer malignancy via ferroptosis activation.
Wu Y, Chen H, Jiang S … +3 more , Wu X, Li D, Xie K
Neoplasma · 2025 Aug · PMID 40958522 · Publisher ↗
Growing evidence indicates that ferroptosis is pivotal in the development and progression of ovarian cancer (OC). However, the function of EGLN2 in OC remains unclear. In this study, we observed that EGLN2 is expressed a...
Growing evidence indicates that ferroptosis is pivotal in the development and progression of ovarian cancer (OC). However, the function of EGLN2 in OC remains unclear. In this study, we observed that EGLN2 is expressed at low levels in OC tissues and is associated with a favorable prognosis in early-stage patients based on data from TCGA and GTEx public databases. Compared with those in normal ovarian epithelial cell lines, EGLN2 mRNA and protein levels were significantly lower in OC cell lines. In vitro functional experiments revealed that EGLN2 overexpression reduced proliferation, increased the intracellular levels of iron ions, reactive oxygen species, lipid peroxidation, and mitochondrial oxidative phosphorylation, and inhibited the Warburg effect. Mechanistically, EGLN2 inhibited the expression of HIF-1α, which binds to the promoter of ceruloplasmin (CP), reducing the proliferation of and inducing ferroptosis in OC cells. A subcutaneous xenograft model in nude mice demonstrated that EGLN2 overexpression inhibited HIF-1α, promoted ferroptosis, and inhibited OC cell growth. In summary, EGLN2 suppressed CP transcription and increased ferroptosis in OC cells. These findings provide new insights into OC development and open avenues for innovative therapies.
ELK1 modulates SF3B3 transcriptional activity to stimulate proliferation and inhibit apoptosis in gastric cancer through the activation of the MAPK pathway.
Zhang Y, Gao L, Liu L … +1 more , Chen H
Neoplasma · 2025 Aug · PMID 40958521 · Publisher ↗
Gastric cancer (GC) ranks as the fifth most common malignancy globally. Aberrant alternative splicing is implicated in tumorigenesis and progression. SF3B3, a key subunit of the spliceosome complex, is closely linked to...
Gastric cancer (GC) ranks as the fifth most common malignancy globally. Aberrant alternative splicing is implicated in tumorigenesis and progression. SF3B3, a key subunit of the spliceosome complex, is closely linked to alternative splicing dysfunction when its expression is dysregulated. This study delved into SF3B3's role and mechanisms in GC, aiming to uncover novel precision treatment targets. Through TCGA database analysis, SF3B3 was found to be upregulated in GC tissues, associated with poor prognosis and immune infiltration. In vitro experiments included cell culture, transduction, CCK-8, colony formation, scratch, migration, apoptosis assays, cell cycle analysis, and western blot, demonstrating that SF3B3 knockdown curbed GC cell proliferation, migration, and invasion, induced apoptosis and cell cycle arrest, while its overexpression had opposite effects. In vivo xenograft experiments showed that SF3B3 suppression markedly inhibits tumor growth. Transcriptome analysis and western blot suggested that SF3B3 promotes GC cell proliferation and impedes apoptosis by activating the MAPK pathway. Moreover, transcription factor ELK1 was shown to regulate SF3B3 expression, with a significant positive correlation between them. Overall, SF3B3 likely drives GC progression via the ELK1-SF3B3-MAPK axis, representing a potential precision treatment target for GC.
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