Cancer Biol. Ther. [JOURNAL]
Sun
200 papers
Unraveling the dual role of METTL3-mediated mA RNA modification in bladder cancer: mechanisms, therapeutic vulnerabilities, and clinical implications.
Chun H, Baima K
Cancer Biol Ther · 2025 Dec · PMID 40778544 · Full text
Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, includ...
Bladder cancer (BC) remains challenging due to its recurrence and metastasis, with METTL3-mediated m A RNA modification emerging as a key oncogenic driver. This review synthesizes METTL3's roles in BC progression, including tumor initiation, metastasis, stemness, and therapy resistance. We detail its regulation of critical pathways (e.g. HIF1A/IGF2BP3/BIRC5, AFF4/NF-κB/c-MYC) and dual functions in RNA stability and epigenetic crosstalk with DNA methylation. METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.
NR4A3 regulates anoikis resistance and metastasis of bladder cancer through EWSR1.
Fan L, Zhou Y, Liu S … +9 more , Zhuo X, Qu L, Wu D, Wang S, Pan X, Zhao T, Xu F, Ge J, Zhou W
Cancer Biol Ther · 2025 Dec · PMID 40762284 · Full text
Bladder cancer (BLCA) is a common urinary malignancy with high metastatic potential. However, the mechanisms underlying its progression remain unclear. This study aimed to investigate the role and regulatory mechanisms o...
Bladder cancer (BLCA) is a common urinary malignancy with high metastatic potential. However, the mechanisms underlying its progression remain unclear. This study aimed to investigate the role and regulatory mechanisms of NR4A3, a nuclear receptor involved in apoptosis and tumor suppression, in BLCA progression, particularly its impact on anoikis resistance and metastasis. NR4A3 expression levels were analyzed using the GEPIA database. Functional studies were conducted by overexpressing NR4A3 in adherent and suspension-cultured BLCA cells. Apoptosis, invasion, migration, and ER stress marker (Bip and CHOP) expression were evaluated. Subcutaneous and lung metastasis models in BALB/c nude mice were used for in vivo validation. GEPIA analysis showed that NR4A3 is significantly downregulated in BLCA. NR4A3 overexpression increased apoptosis, reduced invasion and migration, and upregulated Bip and CHOP expression. , NR4A3 overexpression significantly reduced lung metastasis in BALB/c nude mice ( = 8 per group, < .001). Mechanistically, NR4A3 promoted ER stress by regulating the EWSR1/Ezrin pathway, thereby suppressing anoikis resistance. NR4A3 functions as a tumor suppressor in BLCA by enhancing endoplasmic reticulum stress and inhibiting anoikis resistance through the EWSR1/Ezrin pathway. It may serve as a promising therapeutic target for metastatic BLCA.
Dual role of CXCL10 in cancer progression: implications for immunotherapy and targeted treatment.
Madkhali OA, Moni SS, Almoshari Y … +2 more , Sabei FY, Safhi AY
Cancer Biol Ther · 2025 Dec · PMID 40760734 · Full text
CXCL10 is a chemokine crucial for immune cell recruitment and inflammation modulation, especially within the tumor microenvironment. This review critically analyzes the underexplored role of CXCL10 in modulating JAK/S...
CXCL10 is a chemokine crucial for immune cell recruitment and inflammation modulation, especially within the tumor microenvironment. This review critically analyzes the underexplored role of CXCL10 in modulating JAK/STAT, MAPK/ERK, and PI3K/Akt pathways across different tumor types, highlighting inconsistencies in current research and proposing novel therapeutic strategies based on research from databases such as PubMed and Scopus. Future targeted therapies could include personalized approaches that either enhance the immunostimulatory functions of CXCL10 or inhibit its tumor promoting effects. Techniques such as CRISPR/Cas9-mediated knockout of CXCL10 has demonstrated potential in preclinical models to reduce tumor-promoting inflammation, while nanoparticle-based CXCL10 inhibitors enhance immune checkpoint blockade efficacy in melanoma. In addition, targeting CXCL10-related mechanisms of immune evasion such as inhibition of CXCR3 may help to prevent metastasis. Futureresearch should focus on CXCL10-targeting approaches in highly immunosuppressive tumors, such as pancreatic and glioblastoma, where immune checkpoint inhibitors have shown limited efficacy.
Advancements in exosome-based cancer diagnosis: from chipsets to nano vaccine.
Mukerjee N, Sarkar S, Uti DE … +1 more , Sharma PK
Cancer Biol Ther · 2025 Dec · PMID 40754671 · Full text
Exosome-based therapies represent a pioneering frontier in cancer treatment, leveraging the natural cellular communication mechanisms encapsulated in exosomes. These nano-sized vesicles serve as carriers of proteins, lip...
Exosome-based therapies represent a pioneering frontier in cancer treatment, leveraging the natural cellular communication mechanisms encapsulated in exosomes. These nano-sized vesicles serve as carriers of proteins, lipids, and nucleic acids, reflecting the physiological state of their cells of origin, which makes them ideal candidates for targeted cancer therapies and diagnostics. Despite their potential, the path to clinical application is fraught with challenges. This review explores the inherent challenges associated with exosome-based cancer vaccines, focusing on tumor heterogeneity, the technical difficulties in exosome isolation and characterization, the need for standardized protocols, and the scalability of production methods. It also explores the interaction between exosomes and the immune system, a crucial factor in developing effective cancer vaccines. The review explores strategies to improve diagnostic tools, targeted delivery systems, and therapy based on individual tumor profiles, highlighting the need for innovative approaches and collaborative efforts to maximize exosome-based cancer vaccines' therapeutic potential.
A comparison of cell death pathways in three different kinds of human lung cancer cell lines following hematoporphyrin derivative-mediated photodynamic therapy.
Ma Y, Xiao B, Sui A … +4 more , Yang X, Cui S, Cao Y, Lin C
Cancer Biol Ther · 2025 Dec · PMID 40751929 · Full text
This study was conducted to investigate the in vitro differences in killing effects and cellular death pathways in human bronchial epithelial BEAS-2B cells, human lung adenocarcinoma A549 cells, human lung squamous carci...
This study was conducted to investigate the in vitro differences in killing effects and cellular death pathways in human bronchial epithelial BEAS-2B cells, human lung adenocarcinoma A549 cells, human lung squamous carcinoma H520 cells, and human lung small cell carcinoma H446 cells mediated by hematoporphyrin derivative (HPD) at 630 nm laser wavelength. Our results showed that the viability of the BEAS-2B, A549, H520, and H446 cells gradually decreased with increasing HPD concentration after HPD-PDT. HPD-PDT induced an increase in intracellular ROS production ( < 0.05), with H520 > A549 > H446 > BEAS-2B. HPD-PDT resulted in intracellular chromatin fixation and dense nuclear staining and induced apoptosis, with apoptosis rates of H520 > A549 > H446 > BEAS-2B. The western blotting (WB) results showed that HPD-PDT could lead to reduced BCL-2 protein levels, upregulate BAX protein expression and activate caspase-3 protein, and induce autophagy, as evidenced by the increased expression of the autophagy-related proteins ATG5, Beclin-1 and LC3B in all cells tested. However, apoptosis-inducing proteins and autophagy proteins were statistically different in these four cell types. Our study confirms that HPD-mediated phototoxicity varied in the different cell lines, indicating that lung cancer cells die due to the interactions of different cell death pathways rather than the same well-defined mechanisms.
Cooperative CCL2/CCR2 and HGF/MET signaling enhances breast cancer growth and invasion associated with metabolic reprogramming.
Fang W, Kozai Y, Acevedo DS … +10 more , Brodine R, Gorrepati HS, Arviso N, Cote P, Thompson A, Gerdes Z, Espinoza A, Bergeron N, Brownfield A, Cheng N
Cancer Biol Ther · 2025 Dec · PMID 40736024 · Full text
With over 60,000 cases diagnosed in women annually, ductal carcinoma in situ (DCIS) is the most common form of pre-invasive breast cancer in the US. Despite standardized therapy, under-treatment and over-treatment are pr...
With over 60,000 cases diagnosed in women annually, ductal carcinoma in situ (DCIS) is the most common form of pre-invasive breast cancer in the US. Despite standardized therapy, under-treatment and over-treatment are prevailing concerns. By understanding the mechanisms regulating DCIS progression, we may develop tailored strategies to improve treatment. CCL2/CCR2 and HGF/MET signaling pathways are upregulated in breast cancers. Our studies indicate that these pathways cooperate to promote DCIS progression and metabolism. DCIS and IDC tissues were immunostained for CCL2 and HGF expression. DCIS.com and HCC1937 cells were analyzed for cell proliferation through PCNA immunostaining, apoptosis through cleaved caspase-3 immunostaining, and invasion through Matrigel transwell assays. AKT, AMPK, p42/44MAPK and PKC activities were analyzed in vitro through immunoblot and pharmacologic inhibition. CCL2 and HGF-mediated metabolism were analyzed by LC-MS. Glucose uptake and lactate production were measured biochemically. CCR2 and MET were targeted in breast xenografts through CCR2 knockout and treatment with Merestinib. Significant associations between CCL2 and HGF were detected in DCIS and IDC tissues. CCL2 and HGF co-treatment enhanced breast cancer cell growth, survival, and invasiveness over individual CCL2 or HGF treatment. These CCL2/HGF-mediated phenotypes were associated with metabolic changes including glycolysis and increased AKT, AMPK, p42/44MAPK and PKC signaling. CCL2/HGF-mediated glycolysis was reduced with AKT, AMPK and p42/44MAPK inhibition. CCR2 knockout combined with Merestinib treatment inhibited growth, survival, and stromal reactivity of breast xenografts more than CCR2 or MET targeting alone. CCL2/CCR2 and HGF/MET cooperate to enhance breast cancer progression and metabolic reprogramming.
Copper death combination therapy: the innovative frontier and challenges in prostate cancer treatment.
He JW, Li PZ, Huang ZX
Cancer Biol Ther · 2025 Dec · PMID 40660923 · Full text
Prostate cancer (PCA) remains a significant health challenge, necessitating the exploration of novel therapeutic strategies to enhance patient outcomes. Recent research has identified cuproptosis, a copper-dependent prog...
Prostate cancer (PCA) remains a significant health challenge, necessitating the exploration of novel therapeutic strategies to enhance patient outcomes. Recent research has identified cuproptosis, a copper-dependent programmed cell death mechanism, as a promising target in PCA treatment. Elevated copper levels have been associated with tumor progression and therapeutic resistance, highlighting the need for innovative approaches. This review synthesizes current findings on the role of copper and cuproptosis in PCA, focusing on the mechanisms underlying cuproptosis, the identification of key biomarkers, and the therapeutic potential of copper complexes and ionophores. The integration of cuproptosis-related biomarkers into clinical practice may facilitate personalized treatment strategies, while ongoing research into copper-based therapies holds promise for overcoming limitations of traditional chemotherapy. Future directions should emphasize elucidating the molecular mechanisms of cuproptosis and optimizing therapeutic applications to improve patient outcomes in PCA.
Lenvatinib promotes hepatocellular carcinoma pyroptosis by regulating GSDME palmitoylation.
Yuan Y, Wang MR, Ding Y … +4 more , Lin Y, Xu TT, He XX, Li PY
Cancer Biol Ther · 2025 Dec · PMID 40653759 · Full text
Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be...
Lenvatinib, as a multi-kinase inhibitor, has been approved as a first-line drug for patients with advanced hepatocellular carcinoma (HCC). Gasdermin E (GSDME)-mediated pyroptosis, a form of programmed cell death, can be induced by chemotherapy drugs or certain kinase inhibitors. However, the role of Lenvatinib in inducing pyroptosis in HCC warrants further investigation. Phase contrast microscopy, LDH assays, and gain- and loss-of-function strategies were used to evaluate Lenvatinib-induced pyroptosis in HCC cells. GSDME palmitoylation was assessed via the acyl-biotin exchange method. In vivo, a subcutaneous HCC xenograft model in nude mice were established to assess the effects of interfering with GSDME on the sensitivity of HCC to Lenvatinib. Lenvatinib induced pyroptosis in HCC cells in a dose- and time-dependent manner. Additionally, Lenvatinib promoted GSDME cleavage, with upregulation of GSDME enhancing pyroptosis and downregulation reducing this effect. The ABE method revealed that GSDME is palmitoylated, and Lenvatinib increased its palmitoylation, promoting plasma membrane localization and enhancing protein stability. Inhibition of GSDME palmitoylation by 2-BP blocked Lenvatinib-induced pyroptosis. In vivo, upregulation of GSDME increased HCC sensitivity to Lenvatinib and inhibited tumor growth. Lenvatinib induces pyroptosis in HCC by promoting the palmitoylation of GSDME, enhancing its localization to the plasma membrane and increasing its protein stability. Interfering with GSDME, both in vitro and in vivo, affects Lenvatinib-induced pyroptosis, thereby altering the therapeutic sensitivity of HCC to Lenvatinib. Targeting GSDME palmitoylation represents a potential therapeutic strategy for HCC, as it enhances Lenvatinib-induced pyroptosis and improves the therapeutic response.
Robust prediction of glioma prognosis by hypoxia-induced ferroptosis genes: VEGFA-XBP1 co-expression for salvage therapy.
Liwei Z, Hanwen L, Wenpeng Z … +10 more , Weijie Y, Sifang C, Bingchang Z, Zhangyu L, Xin G, Wenhua L, Jianyao M, Yuanyuan X, Guowei T, Zhanxiang W
Cancer Biol Ther · 2025 Dec · PMID 40621799 · Full text
Hypoxia as a hallmark of solid malignancies compromises therapeutic efficacy and prognosis. This study deciphers the functional role of hypoxia-induced ferroptosis in glioma prognosis. Hypoxia-related transcripts and fer...
Hypoxia as a hallmark of solid malignancies compromises therapeutic efficacy and prognosis. This study deciphers the functional role of hypoxia-induced ferroptosis in glioma prognosis. Hypoxia-related transcripts and ferroptosis markers were curated from public databases. ConsensusClusterPlus identify hypoxia-based molecular subtypes, while LASSO-penalized Cox regression integrated with limma-based differential expression analysis screened prognostic ferroptosis genes. Subsequent risk modeling was validated against clinical parameters and extended through nomogram construction. Protein-protein interaction networks centered on HIF-1αidentified high-confidence interactors, with parallel immune correlation analysis completing the systems-level investigation.Based on 27 hypoxia-associated genes, we stratified samples into three distinct hypoxic clusters. Differential analysis of 123 ferroptosis markers across clusters, combined with univariate Cox regression and LASSO regression, identified 23 hypoxia-induced ferroptosis genes for constructing a prognostic model. The model demonstrated robust predictive accuracy with AUC values of 0.80 (1-year), 0.86 (3-year), and 0.86 (5-year). GSEA revealed significant enrichment in ECM-receptor interactions, focal adhesion, JAK-STAT signaling, and p53 signaling pathways, suggesting their involvement in hypoxia-induced ferroptosis. Our risk model significantly outperformed conventional clinical parameters (pathology, grade, age, primary/recurrent status). Protein-protein interaction analysis incorporating HIF-1αand the 23-model genes identified XBP1 and VEGFA co-expression as significant positive prognostic factor. The immune infiltration analysis further indicated that M0 macrophages may participate in the regulation of the prognosis of VEGFA-XBP1.Hypoxia-induced ferroptosis modulation emerges as a prognostic factor in gliomas, with XBP1 and VEGFA representing druggable nodes for novel combination therapies.
USP44 promotes chemotherapeutic drug resistance of triple negative breast cancer through EZH2 protein stability.
Wu P, Xiao W, Ni J … +2 more , Lou Y, Xu C
Cancer Biol Ther · 2025 Dec · PMID 40619273 · Full text
Triple negative breast cancer (TNBC), a highly invasive breast cancer, is one of the leading causes of cancer-related mortality worldwide. Although chemotherapy remains the standard of care for TNBC, the development of c...
Triple negative breast cancer (TNBC), a highly invasive breast cancer, is one of the leading causes of cancer-related mortality worldwide. Although chemotherapy remains the standard of care for TNBC, the development of chemotherapy resistance significantly limits its clinical efficacy. In this study, we identified the deubiquitinating enzyme USP44 as a contributor to chemoresistance in TNBC and investigated the potential regulatory feedback mechanisms involved. In this experimental study, we investigated the sensitivity of TNBC cells MDA-MB-231 and BT-549 to chemotherapy drugs after overexpression and knockdown of USP44 using CCK-8 reagent kit and flow cytometry analysis, respectively. Western blot was performed to evaluate the expression levels of relevant proteins. In vivo xenograft models were established to examine the effects of USP44 and its downstream targets on chemosensitivity. Co-immunoprecipitation assay and ubiquitination assay were conducted to identify interacting proteins and elucidate the underlying molecular mechanisms. Knockdown of USP44 increased the sensitivity of MDA-MB-231 and BT-549 cells to chemotherapeutic agents, accompanied by elevated levels of Cleaved PARP. In contrast, USP44 overexpression reduced drug sensitivity. Mechanistically, USP44 was found to interact with EZH2, preventing its ubiquitination and subsequent proteasomal degradation. Notably, treatment with GSK126, a specific EZH2 inhibitor, reversed the chemoresistance induced by USP44 overexpression. USP44/EZH2 signaling pathway is one of the key to causing the drug resistance of TNBC, warranting further clinical investigation.
IFN-γ downregulates miR-4319 to enhance NLRC5 and MHC-I expression in MHC-I-deficient breast cancer cells.
Zhao MZ, Zheng HC, Sun Y … +5 more , Jiang XF, Liu L, Dang CY, Li JY, Sun LX
Cancer Biol Ther · 2025 Dec · PMID 40596738 · Full text
Sufficient MHC-I expression on cancer cells is essential for the recognition and killing of cancer cells by immune effector cytotoxic T-lymphocyte (CTL). An important mechanism of cancer immune escape is loss or down-reg...
Sufficient MHC-I expression on cancer cells is essential for the recognition and killing of cancer cells by immune effector cytotoxic T-lymphocyte (CTL). An important mechanism of cancer immune escape is loss or down-regulation of MHC-I. This is frequently associated with reduced expression of NOD-like receptor (NLR) caspase recruitment domain containing protein 5 (NLRC5), genetically and epigenetically. NLRC5, a regulator of MHC-I, has been identified as a potential target of miR-4319 due to its complementary binding site for miR-4319, according to prediction by TargetScan (http://www.targetscan.org/). Inhibition of miR-4319 by IFN-γ (known as MHC-I increasing agent) to upregulate NLRC5 with upregulation of MHC-I in MHC-I-deficient breast cancer cells, however, remains unclear. After treatment with IFN-γ, miR-4319 was detected with qRT-PCR; NLRC5 protein was detected with western-blot; and MHC-I mRNA and protein were detected with qRT-PCR and western-blot, respectively. It was found statistically that miR-4319 was lower and NLRC5 protein was higher in groups of 50 U/ml and 100 U/ml IFN-γ, and MHC-I mRNA and protein were higher in all groups of different concentrations of IFN-γ, except for HLA-A protein in 25 U/ml IFN-γ group, with dose dependent tendency, compared with the control group. IFN-γ inhibits miR-4319 and upregulates NLRC5, thereby enhancing expression of MHC-I in SKBR3 breast cancer cells, while limitations include the absence of functional rescue experiments and in vivo validation. Along with direct cytotoxicity on tumor cells, IFN-γ's immunomodulatory effect strengthens tumor immunogenicity, counteracts immune evasion mechanisms, and potentially improves the efficacy of cancer immunotherapy.
Highly enriched exosomal lncRNA OIP5-AS1 regulates gastrointestinal stromal tumor (GIST) resistance to sunitinib through miR-145 and SOX9.
Wang CH, Yao XM, Pan CX … +2 more , Zhan HF, Zhou HF
Cancer Biol Ther · 2025 Dec · PMID 40548429 · Full text
Targeted therapy-induced resistance is a significant factor contributing to treatment failure in patients with gastrointestinal stromal tumors (GIST). Despite the identification of the long non-coding RNA (lncRNA) OIP5-A...
Targeted therapy-induced resistance is a significant factor contributing to treatment failure in patients with gastrointestinal stromal tumors (GIST). Despite the identification of the long non-coding RNA (lncRNA) OIP5-AS1 as a critical player in human malignancy development, its role in GIST-related drug resistance remains largely unexplored. This study revealed substantial up-regulation of both OIP5-AS1 and SOX9, alongside significant down-regulation of miR-145, within sunitinib-resistant GIST cells. OIP5-AS1 emerged as a competing endogenous RNA, exerting inhibition on miR-145 while concurrently promoting the expression of SOX9. Exosome-mediated transfer of OIP5-AS1 induced heightened proliferation and invasion of GIST cells, culminating in the induction of chemoresistance to sunitinib through the miR-145/SOX9 axis. The knockdown of OIP5-AS1-expressing exosomes resulted in reduced cell proliferation and invasion in chemo-resistant GIST cells. In summary, these findings collectively suggest that OIP5-AS1 fosters GIST cell proliferation and invasion by suppressing miR-145 and up-regulating SOX9, ultimately contributing to drug resistance and tumor progression in GIST.
β-hydroxybutyrate, a ketone body, suppresses tumor growth, stemness, and invasive phenotypes in non-small cell lung cancer.
Huang Y, Ding J, Zhu Y … +5 more , Shi J, Liu R, Wu C, Han L, Zhang M
Cancer Biol Ther · 2025 Dec · PMID 40545696 · Full text
Lung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in vari...
Lung cancer is the most common cancer worldwide. The stemness and metastasis of tumor cells present major challenges to effective lung cancer treatment. Beta-hydroxybutyrate (BHB), a ketone body, plays a key role in various cancers. However, whether BHB mediates the progression of non-small cell lung cancer (NSCLC) remains unclear. The effects of BHB on the proliferation, apoptosis, and metastasis of NSCLC cells were assessed using the Cell Counting Kit 8, flow cytometry, western blotting, and Transwell assays. The sphere formation assay was used to evaluate the impact of BHB on NSCLC cell stemness. The underlying molecular mechanism was investigated through knockdown and overexpression of free fatty acid receptor 3 (FFAR3) using shRNAs and expression vectors in two NSCLC cell lines (NCI-H1975 and PC-9). , xenograft tumor and liver metastasis models were established in nude mice. BHB treatment reduced viability, stemness, and migratory and invasive abilities of NSCLC cells. BHB also induced apoptosis and increased cleaved caspase-3 levels in these cells. Moreover, BHB suppressed tumor growth and metastasis, and reduced cell stemness in NSCLC tissues . Mechanistically, FFAR3 knockdown abolished, while FFAR3 overexpression enhanced, the tumor-suppressive effects of BHB, identifying FFAR3 as a key mediator. These data shed light on the role of BHB in NSCLC development and its underlying molecular mechanisms, suggesting a promising treatment strategy for patients with NSCLC.
Unresectable ectopic hepatocellular carcinoma in the left sub-diaphragmatic area and retroperitoneum treated with TACE: case report and literature review.
Xie CB, Tang ZJ, Wu Y … +1 more , Zhao KF
Cancer Biol Ther · 2025 Dec · PMID 40542673 · Full text
Ectopic hepatocellular carcinoma (EHCC) demonstrates morphological and immunohistochemical features identical to conventional intrahepatic hepatocellular carcinoma (HCC), originating from ectopic liver tissue (EL), which...
Ectopic hepatocellular carcinoma (EHCC) demonstrates morphological and immunohistochemical features identical to conventional intrahepatic hepatocellular carcinoma (HCC), originating from ectopic liver tissue (EL), which is defined as a hepatic organ or tissue not connected to the mother liver. EHCC is a rare disease and difficult to diagnose preoperatively. Therefore, its epidemiology, treatment, and prognosis are not fully elucidated. Herein, we present a case report of a 52-year-old male diagnosed with unresectable EHCC who underwent transarterial chemoembolization (TACE) and succumbed to the disease 13 months after treatment, accompanied by a literature review summarizing the epidemiology while analyzing therapeutic strategies and prognostic outcomes in EHCC through synthesis of published case evidence.
Correction.
Cancer Biol Ther · 2025 Dec · PMID 40517282 · Full text
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The small molecule drug CBL0137 interferes with DNA damage repair and enhances the sensitivity of NK/T-Cell lymphoma to cisplatin.
Gu H, Qian S, Zhang Y … +3 more , Zhang M, Chen Q, Zhang X
Cancer Biol Ther · 2025 Dec · PMID 40419449 · Full text
This study aimed to investigate the in vitro and in vivo antitumor effects and mechanisms of the small molecule anticancer drug CBL0137 in NK/T-cell lymphoma (NKTCL), as well as its efficacy when combined with chemothera...
This study aimed to investigate the in vitro and in vivo antitumor effects and mechanisms of the small molecule anticancer drug CBL0137 in NK/T-cell lymphoma (NKTCL), as well as its efficacy when combined with chemotherapy or immunotherapy. Cell viability assays were performed to evaluate the inhibitory effect of CBL0137 on NKTCL cell proliferation in vitro. Flow cytometry was used to assess the effects of the drug on apoptosis and cell cycle progression. RNA sequencing (RNA-seq) was employed to explore the mechanism of action of CBL0137 in NKTCL, and Western blotting (WB) was used to validate the expression of related proteins. An in vivo xenograft model was used to confirm the antitumor activity of CBL0137. Additionally, immunohistochemistry analysis was conducted to further study tumor tissue. CBL0137 effectively inhibited the proliferation of NKTCL cells in vitro, induced apoptosis, and significantly blocked cell cycle progression. RNA-seq analysis revealed that CBL0137 exerts its antitumor effect primarily by interfering with DNA damage repair. In vivo experiments using xenografted mice confirmed the antitumor activity of CBL0137. CBL0137, when combined with PD-1 antibody, exhibits synergistic antitumor effects in mice, and its combination with cisplatin significantly enhances the sensitivity of NKTCL to cisplatin. CBL0137 inhibits DNA damage repair in NK/T-cell lymphoma and enhances its sensitivity to cisplatin.
Lung cancer cell derived sEVs enhance the metastasis of non-small cell lung cancer via SNHG12/miR-326/SLC7A11 axis.
Liu Y, Zhang L, Wang J … +4 more , Xu J, Xu J, Xie M, Wang R
Cancer Biol Ther · 2025 Dec · PMID 40417819 · Full text
Abnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Trans...
Abnormally expressed long non-coding (lnc)RNAs are closely associated with the pathogenesis of non-small cell lung cancer (NSCLC); thus, the present study aimed to investigate the potential role of SNHG12 in NSCLC. Transmission electron microscopy and nanoparticle tracking analysis were conducted to verify NSCLC cell-derived small extracellular vesicles (sEVs). MicroRNA (miRNA/miR) and mRNA expression levels were determined using reverse transcription-quantitative PCR, while protein expression levels were determined using western blot analysis and immunofluorescence. In addition, potential binding sites between miR-326 and SNHG12/SLC7A11 were verified using a dual-luciferase reporter assay. Cell behavior was detected using flow cytometry, colony formation, wound healing and Transwell assays, and xenograft experiments were conducted to confirm the roles of SNHG12 in NSCLC. H&E staining was used for histological analysis, and each experiment was repeated three times. Results of the present study demonstrated that NSCLC-derived SNHG12 promoted type-2 tumor-associated macrophage (TAM2) polarization. However, the decrease of SNHG12 expression in EVs reduced TAM2 polarization, weakened NSCLC cell proliferation, migration and invasion, and promoted tumor cell ferroptosis. Moreover, results of the present study revealed that SNHG12 knockdown markedly suppressed tumor growth and the metastasis of NSCLC. In addition, SNHG12 upregulated SLC7A11 expression via binding to miR-326. Overexpressed SLC7A11 promoted tumor aggressiveness and suppressed the ferroptosis of NSCLC cells. Collectively, results of the present study revealed that SNHG12 suppressed ferroptosis and promoted the metastasis of NSCLC, further demonstrating that high SNHG12 expression levels may be indicative of poor clinical outcomes for patients with NSCLC. Thus, the present study highlighted that the SNHG12/miR-326/SLC7A11 axis may exhibit potential as a novel target for the treatment of NSCLC.
Suppression of pseudogene MT2P1 transcription induced by E2F7 inhibits hepatocellular carcinoma cell proliferation and facilitates apoptosis via preserving its parental gene.
Lu Y, Zhang Y, Hao F … +3 more , Wang N, Chen Y, Wang J
Cancer Biol Ther · 2025 Dec · PMID 40407049 · Full text
The majority of the pseudogenes are inert in normal transcription. Their transcripts are mostly attributed to non-coding RNAs that play various functions in human tumorigenicity and progression. Distinctively, pseudogene...
The majority of the pseudogenes are inert in normal transcription. Their transcripts are mostly attributed to non-coding RNAs that play various functions in human tumorigenicity and progression. Distinctively, pseudogene MT2P1 is universally transcribed in hepatocytes and presents a significant decrease in hepatocellular carcinoma (HCC). The effect of MT2P1-RNA on HCC cell proliferation and apoptosis needs investigation. MT2P1-RNA was detected by RT-qPCR assay in HCC tissues and cell lines, combined with the exploration of the public databases. The immunohistochemistry assay was used for testing the expression profile of E2F7 and the parental gene MT2A. The clinicopathological features of the patients were collected and analyzed. Ectopic expression of MT2P1-RNA in HCC cell lines was conducted, and the CCK8 assay and flow cytometry assay were carried out. Chromatin immunoprecipitation assay and Dual-luciferase reporter assay were, respectively, applied to validate the interaction between MT2P1, E2F7, and microRNA-15b-5p. The downregulation of MT2P1-RNA in HCC is negatively correlated with dismal clinicopathological features. MT2P1-RNA significantly suppressed HCC cell proliferation and induced apoptosis. E2F7 depletion sequentially elevated the level of MT2P1-RNA and MT2A, and E2F7 was validated as a suppressive transcription factor of the MT2P1 gene. The direct interactions of either MT2P1/miR-15b-5p or miR-15b-5p/MT2A were, respectively, ascertained, enlightening the ceRNA effect of them. The pseudogene-derived MT2P1-RNA is a suppressor of HCC by exerting the ceRNA effect on preserving MT2A, and its transcription is regulated by the suppressive transcription factor E2F7.
Efficacy of brachytherapy for locally advanced bladder cancer: a single-center retrospective clinical study.
Han X, Chen H, Wang B
Cancer Biol Ther · 2025 Dec · PMID 40405409 · Full text
To explore the feasibility, safety, and effectiveness of brachytherapy of locally advanced bladder cancer, clinical data of 86 patients with locally advanced bladder cancer treated in the Department of Urology Surgery, S...
To explore the feasibility, safety, and effectiveness of brachytherapy of locally advanced bladder cancer, clinical data of 86 patients with locally advanced bladder cancer treated in the Department of Urology Surgery, Shanxi Provincial Cancer Hospital, between January 2015 and June 2019 were analyzed retrospectively. The patients were categorized into the study ( = 45) and control ( = 41) groups according to the treatment methods. Patients in the study group were treated with brachytherapy (intraoperative implantation of radioactive particles) + neoadjuvant chemotherapy (NAC), and those in the control group were treated with NAC. Patients in both groups underwent radical cystectomy (RC) + pelvic lymph node dissection. Postoperative pathological examinations proved that patients in both groups had urothelial carcinoma at stage pT-pT. The endpoints included 3-y locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), and adverse events after treatment. The efficacy and safety of interstitial implantation of radioactive particles for the treatment of locally advanced bladder cancer were assessed. The patients were followed up for 9-42 months. The 3-y LRFS was significantly higher in the study group (88.9%) than in the control group (60.9%) ( = .003). The 3-y DMFS in the study group (71.1%) and the control group (73.2%) was statistically similar ( = .945). The 3-y DFS and OS were not statistically significant between the two groups (DFS: study group 64.4% . control group 51.2%, = .073; OS: study group 66.7% . control group 58.5%, = .180). Local shifting of the particles was detected in three patients at 1 week to 1 month after the operations in the study group, but no related complications were observed. Blood events (anemia, leukocytopenia, and thrombocytopenia), liver and renal dysfunction, vomiting, diarrhea, and weakness were the major adverse reactions, which were alleviated after symptomatic treatments. The results have not statistically significant differences between the two groups in major adverse reactions. Compared to the NAC group, brachytherapy + NAC significantly prolongs the LRFS of patients with locally advanced urothelial bladder carcinoma who underwent RC + pelvic lymph node dissection. This surgery increases the LRFS, develops better personalized treatment plans, and improves treatment effectiveness. In addition, the treatment is safe and effective, with only limited adverse effects.
Inhibitory effect of Endostar on HIF-1 with upregulation of MHC-I in lung cancer cells.
Zhao MZ, Zheng HF, Wang JN … +3 more , Zhang YM, Wang HJ, Zhao ZW
Cancer Biol Ther · 2025 Dec · PMID 40392714 · Full text
Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy fo...
Endostar is a human recombinant endostatin which is an attractive anti-angiogenesis protein. Because inefficient antigen presenting MHC class I expression (which can be downregulated by HIF-1) is an important strategy for cancer immune evasion, besides its anti-angiogenesis effect, it remains unclear whether Endostar has an inhibitory effect on HIF-1 expression by upregulating MHC class I expression in cancer cells to facilitate immunotherapies, including PD-1/PD-L1 inhibitors. In this study, A549 and NCI-H1299 lung cancer cells were treated with Endostar (6.25 μg/ml, 12.5 μg/ml, and 25 μg/ml, respectively). HIF-1 expression was detected by Immunocytochemistry and Western blot. Proteins of the MHC class I α-heavy chain and β2 m light chain, STAT3 and pSTAT3 were detected by Western blot. The mRNAs of MHC class I α-heavy chain and β2 m light chain were detected by RT-qPCR. It was shown that decreased expression of HIF-1 and promotion of β2-microglobulin were observed after Endostar treatment. In addition, elevated levels of MHC class I α-heavy chain mRNA and protein, as well as downregulation of STAT3 and pSTAT3, were also observed following Endostar treatment. Endostar inhibited HIF-1 expression in A549 and NCI-H1299 lung cancer cells, upregulated expression of MHC class I α-heavy chain and β2 m light chain, with the upregulation of STAT3 and pSTAT3, suggesting involvement of STAT3 pathway. It is important because only in combination with MHC class I on target cells can tumor antigenic peptides be recognized by CD8+ CTLs which destroy target cells. However, MHC class I is frequently deficient in cancer cells.
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