Heat shock protein 22 (HSP22) can reduce type 2 diabetes mellitus (T2DM) induced vascular endothelial injury by inhibition of inflammation and oxidative stress. Therefore, we explored whether HSP22 alleviated diabetes ca...Heat shock protein 22 (HSP22) can reduce type 2 diabetes mellitus (T2DM) induced vascular endothelial injury by inhibition of inflammation and oxidative stress. Therefore, we explored whether HSP22 alleviated diabetes cardiomyopathy (DCM) in mice. A T2DM mouse model was constructed and myocardial tissues were used to perform transcriptome sequencing. HSP22 transgenic and HSP22 knockout mice were established to confirm its role in DCM. Transthoracic echocardiography, hematoxylin-eosin staining, TUNEL staining and apoptosis-related proteins were detected to evaluate myocardial injury. Dihydroethidium staining, malondialdehyde and superoxide dismutase levels were detected to evaluate myocardial oxidative stress. We performed RT-PCR to detect inflammatory factors and evaluate the myocardial inflammatory response. Immunohistochemical staining, RT-PCR and western blot were used to define the expression of HSP22 in mouse myocardial tissues. Transcriptome sequencing analysis revealed the expression of HSP22 in myocardium of T2DM mice significantly decreases. GO analysis found that oxidative stress and inflammatory response were closely related to DCM in mice. Furthermore, HSP22 overexpression can alleviate DCM in mice and HSP22 knockout aggravated DCM. HSP22 reduced oxidative stress and inflammation to alleviate DCM in mice.
The clinical outcomes of acute myeloid leukemia (AML) patients exhibit substantial heterogeneity, with relapse posing a formidable challenge. Herein, we developed a risk score model by integrating relapse-related genes t...The clinical outcomes of acute myeloid leukemia (AML) patients exhibit substantial heterogeneity, with relapse posing a formidable challenge. Herein, we developed a risk score model by integrating relapse-related genes through Cox regression analysis. The relapse-related genes were identified via differential gene expression analysis of 15 matched diagnosed and relapsed AML samples retrieved from the Gene Expression Omnibus (GEO) database. These genes include , , , and . Our findings demonstrate that higher risk scores were significantly associated with an unfavorable ELN2017 risk classification, leukemic transformation, as well as -ITD and mutations. Conversely, lower risk scores were linked to mutation. Patients with higher risk scores had a shorter overall survival (OS). Furthermore, we integrated the risk score model with the European LeukemiaNet (ELN) risk classification to establish a novel composite risk classification scheme. Patients were classified into three new risk groups based on composite risk classification showing significantly distinct OS. In summary, the four-gene risk score holds promise in predicting the OS of AML patients, and the composite risk classification shows greater potential in predicting the outcomes of AML patients. These four genes may represent potential therapeutic targets in the treatment of AML.
Bacterial proteins released into the cellular microenvironment are increasingly recognized as pivotal modulators of host key signaling pathways, with significant implications for cellular functions. This review explores...Bacterial proteins released into the cellular microenvironment are increasingly recognized as pivotal modulators of host key signaling pathways, with significant implications for cellular functions. This review explores the multifaceted roles of such bacterial proteins, often functioning as virulence factors, in modulating the host cell cycle. By focusing on the interactions between selected bacterial proteins and essential components of the cell cycle machinery, we describe the mechanisms through which these interactions disrupt relevant cellular functions and contribute to disease development, with a particular focus on cancer.
Stem cells play a critical role in tissue regeneration and the maintenance of homeostasis. Due to their high replicative potential, stem cells face an elevated risk of DNA damage during DNA replication. Consequently, eff...Stem cells play a critical role in tissue regeneration and the maintenance of homeostasis. Due to their high replicative potential, stem cells face an elevated risk of DNA damage during DNA replication. Consequently, efficient DNA damage repair (DDR) mechanisms are essential for preserving the genomic stability and functionality of stem cells. This review summarizes the main DNA damage repair mechanisms, examines the characteristics of these DDR pathways in different stem cell types (highlighting their specific features and key molecules), and discusses the clinical significance and applications of stem cell DDR research. Furthermore, we identify current research limitations and propose potential future research directions. Collectively, this review provides a comprehensive perspective on DDR mechanisms in stem cells, laying a foundation for future investigations and potential clinical applications.
Cyclin-dependent kinases CDK8 and CDK19 together with their activating partner, cyclin C, regulate gene expression as a part of the Mediator complex and by phosphorylating DNA sequence-specific transcription factors. Her...Cyclin-dependent kinases CDK8 and CDK19 together with their activating partner, cyclin C, regulate gene expression as a part of the Mediator complex and by phosphorylating DNA sequence-specific transcription factors. Here, we investigated the requirement for Cdk8 and Cdk19 in hematopoiesis by generating double knockout (DKO) mice lacking Cdk8 and Cdk19 expression in hematopoietic cells. DKO mice displayed relatively normal hematopoiesis and largely unperturbed gene expression in the bone marrow, indicating that the Mediator kinases are not essential for the regulation of gene expression during hematopoiesis. However, DKO mice showed an expansion of splenic macrophages. Bone marrow-derived DKO macrophages displayed an increased expression levels of both M1-like and M2-like markers, altered cytokine secretion, deregulated gene expression, precocious cell cycle exit and impaired Fc-mediated phagocytosis. Our findings reveal a highly cell type-specific role of Cdk8/19 in gene transcription during hematopoiesis.
Breast cancer (BC) is identified as a significant cause of cancer mortality in the female population. The recurrence of initial tumors and the metastasis to remote areas of the body are significant factors leading to the...Breast cancer (BC) is identified as a significant cause of cancer mortality in the female population. The recurrence of initial tumors and the metastasis to remote areas of the body are significant factors leading to the mortality linked with BC. Despite the advancements in diagnostic and therapeutic approaches, a comprehensive understanding of the molecular mechanisms underlying metastasis is still unclear, particularly regarding the regulatory role of non-coding RNAs (ncRNAs) in epithelial-mesenchymal transition (EMT). Different categories of ncRNAs, including microRNAs (miRNAs), circular RNAs (circRNAs), and long ncRNAs (lncRNAs), can manage the complex regulatory frameworks of EMT at various levels. Since dysregulation of ncRNAs is associated with key processes in EMT, investigating them as valuable tools for identifying the metastatic potential of tumors at an early stage could significantly increase diagnostic accuracy and improve patient outcomes, particularly in BC. This review aims to bridge this gap by systematically summarizing current insights into the interplay between EMT and various classes of ncRNAs in the context of BC progression. We discuss the molecular pathways through which ncRNAs regulate EMT, their impact on metastasis and explore their potential as diagnostic biomarkers and therapeutic targets. By providing an integrative overview of recent findings, this article highlights unresolved questions and proposes directions for future research, offering a valuable resource for researchers and clinicians involved in breast cancer biology and treatment development.
Paclitaxel is a widely used chemotherapeutic agent that plays a vital role in the treatment of various cancers, including breast, ovarian, and lung cancers. Despite its success, the development of resistance significantl...Paclitaxel is a widely used chemotherapeutic agent that plays a vital role in the treatment of various cancers, including breast, ovarian, and lung cancers. Despite its success, the development of resistance significantly limits its long-term efficacy. Paclitaxel resistance involves a range of molecular mechanisms, including alterations in drug transport, mutations in β-tubulin, and activation of pro-survival signaling pathways. Recent studies have highlighted the crucial role of circular RNAs (circRNAs) in mediating paclitaxel resistance. CircRNAs are characterized by their stable, covalently closed structures, which protect them from exonuclease degradation. They regulate drug resistance through various mechanisms, including modulating transcription factors and influencing cellular processes such as apoptosis, immune response, and cancer stem cell dynamics by sponging microRNAs. This review focuses on the mechanisms by which circRNAs contribute to paclitaxel resistance and discusses their dual roles as both oncogenes and tumor suppressors. Furthermore, we explore the potential of circRNAs as novel therapeutic targets to overcome paclitaxel resistance. By targeting specific circRNAs or restoring tumor-suppressive circRNAs, it may be possible to enhance paclitaxel sensitivity and improve treatment outcomes. Future research is essential to further understand the role of circRNAs in paclitaxel resistance and to develop effective circRNA-targeted therapies for cancer treatment.
Mutations in cause a spectrum of cholestatic liver disease, ranging from Progressive-Familial-Intrahepatic-Cholestasis type-1 (PFIC1) to Benign-Recurrent-Intrahepatic-Cholestasis type-1 (BRIC1). Manifestations of PFIC1...Mutations in cause a spectrum of cholestatic liver disease, ranging from Progressive-Familial-Intrahepatic-Cholestasis type-1 (PFIC1) to Benign-Recurrent-Intrahepatic-Cholestasis type-1 (BRIC1). Manifestations of PFIC1 include severe pruritus, jaundice, and liver damage. Extrahepatic features sometimes observed in PFIC1 include sensorineural hearing loss, diarrhea, pancreatitis, and short stature. ATP8B1 was shown to translocate phospholipids across the plasma membrane; however, expression of ATP8B1 in many tissues and the range of pathological manifestations in ATP8B1 deficiency suggest diverse physiological functions of ATP8B1, and pleiotropic mechanisms regulating its activity. Recent studies suggest that phosphoinositides, including PIP2 and PIP3, can function as regulators, substrates, and binding partners of ATP8B1. New research shows that ATP8B1 modulates host immune system by regulating cleavage of pyroptotic-executioner Gasdermin D (GSDMD), and inflammation-resolution pathways such as phagocytosis/efferocytosis. Further mechanistic insights can accelerate development of new therapies for restoring membrane integrity, reducing inflammasome activity, and correcting metabolic imbalances caused by ATP8B1 dysfunction.
Ranking second out of new cancer cases, breast cancer (BRCA) is the leading cause of cancerous death among women globally. Methyltransferase-like 3 (METTL3), as the well-known N6‑methyladenosine (m6A) "writer" with catal...Ranking second out of new cancer cases, breast cancer (BRCA) is the leading cause of cancerous death among women globally. Methyltransferase-like 3 (METTL3), as the well-known N6‑methyladenosine (m6A) "writer" with catalytic function, regulates cancer progression through specific downstream targets, but its interplay with epidermal growth factor (EGF) signaling in BRCA is poorly defined. Here, we depict a METTL3-m6A-EGF axis in BRCA, where BRCA cell properties were affected by METTL3 through m6A-dependent expression of EGF. We observed the correlation between METTL3 expression in BRCA tissues and negative prognosis through bioinformatics analysis and RT-qPCR. lentiviral-mediated METTL3 knockdown suppressed proliferation and migration, while the tumor formation experiment in nude mice validated the tumor-promoting effect of METTL3. Hematoxylin-eosin staining and immunohistochemistry also showed the tumor-promoting effect of METTL3. Mechanistically, METTL3 stabilized EGF mRNA via m6A modification, as evidenced by MeRIP-qPCR and Western blotting. Notably, METTL3 maintains EGF/EGFR signaling, and its overexpression leads to insensitivity to gefitinib and adriamycin. We naturally conclude that METTL3 is a central epigenetic regulator of EGF-driven BRCA progression, providing a rationale for targeting METTL3 to overcome chemotherapeutic resistance.
TGFβ functions as a tumor suppressor or promoter, depending on the context, making TGFβ a useful predictive biomarker. Genes related to TGFβ signaling and Aurora kinase were tested for their ability to predict the progre...TGFβ functions as a tumor suppressor or promoter, depending on the context, making TGFβ a useful predictive biomarker. Genes related to TGFβ signaling and Aurora kinase were tested for their ability to predict the progression risk of primary prostate tumors. Using data from The Cancer Genome Atlas (TCGA), we trained an elastic-net regularized Cox regression model including a minimal set of gene expression, copy number (CN), and clinical data. A multi-step feature selection and regularization scheme was applied to minimize the number of features while maintaining predictive power. An independent hold-out cohort was used to validate the model. Expanding from prostate cancer, predictive models were similarly trained on all other eligible cancer types in TCGA. , , and were predictive biomarkers of prostate cancer progression, and upregulation of these genes was associated with promotion of cell-cycle progression. Extending the analysis to other TCGA cancer types revealed a trend of increased predictive performance on validation data when clinical features were complemented with molecular features, with notable variation between cancer types and clinical endpoints. Our findings suggest that TGFβ signaling genes, prostate cancer related genes and Aurora kinases are strong candidates for patient-specific clinical predictions and could help guide personalized therapeutic decisions.
Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenof...Previous studies demonstrated that integrase-strand-transfer-inhibitors (INSTIs) promote adipocyte differentiation, while nucleoside-reverse-transcriptase-inhibitors (NRTIs) tenofovir-alafenamide-fumarate (TAF) and tenofovir-disoproxil-fumarate (TDF), inhibit adipogenesis. NRTIs were shown to counteract the pro-adipogenic effects of INSTIs[6]. However, the effects of non-nucleoside-reverse-transcriptase-inhibitors (NNRTIs) and of the novel long-acting INSTI cabotegravir (CAB), on adipogenesis, alone or in combination with NRTIs or other INSTIs, remain unclear. This study aims to elucidate the impact of NNRTIs and recent INSTIs on adipogenesis. 3T3-L1 cells were used as an adipogenesis in vitro model. The NNRTIs doravirine (DOR) and rilpivirine (RPV) were tested alone and in combination with DTG, CAB, TDF, TAF. Adipogenesis was assessed by Oil-Red-O-staining and by measuring expression-levels of peroxisome-proliferator-activated-receptor-gamma (PPARγ) and CCAAT/enhancer-binding-protein-alpha (C/EBPα). Moreover, Fibroblast-marker ER-TR7 was assessed by immunohistochemistry. CAB, DOR, and RPV promoted adipogenesis, with CAB and DOR showing greater effects. In combination, NNRTIs enhanced the adipogenic effects of CAB and DTG. Conversely, TAF and TDF, when paired with RPV or DOR, inhibited adipogenesis. NNRTIs and CAB increased ER-TR7 expression, suggesting fibroblastic differentiation. Finally, NNRTIs and INSTIs promote adipogenesis and induce fibroblastic features in 3T3-L1 cells. Contrarily, TAF and TDF exhibited an antagonistic effect on adipogenesis when combined with certain antiretrovirals, supporting our previous research.
BACKGROUND: This study aimed to investigate the expression pattern of astrocyte-derived STC1 in TLE and elucidate the molecular mechanisms by which STC1 regulates neuroinflammation and seizures through the NF-κB signalin...BACKGROUND: This study aimed to investigate the expression pattern of astrocyte-derived STC1 in TLE and elucidate the molecular mechanisms by which STC1 regulates neuroinflammation and seizures through the NF-κB signaling pathway. METHODS: A TLE model was established by intrahippocampal injection of kainic acid (KA) in mice. STC1 expression levels and cellular localization in the hippocampus of TLE mice were examined. Adeno-associated virus-mediated gene overexpression and shRNA knockdown approaches were employed to investigate the effects of STC1 on neuroinflammatory responses, neuronal survival, and seizure activity. qRT-PCR and immunofluorescence methods were further utilized to evaluate inflammatory cytokine levels and NF-κB signaling pathway activity. RESULTS: STC1 expression was upregulated in hippocampal tissues of TLE mice, with double immunofluorescence showing STC1 predominantly localized in GFAP-positive reactive astrocytes. STC1 overexpression significantly exacerbated KA-induced neuroinflammation, along with enhanced microglial activation. STC1 knockdown attenuated neuroinflammatory responses. Nissl staining and NeuN immunohistochemistry confirmed that STC1 aggravated KA-induced neuronal loss. STC1 overexpression promoted p65 phosphorylation and nuclear translocation, activating the NF-κB signaling pathway. CONCLUSION: This study reveals the molecular mechanism by which astrocyte-derived STC1 promotes TLE-associated neuroinflammation and neuronal injury through activation of the NF-κB signaling pathway, elucidating the crucial role of the astrocyte-STC1-NF-κB axis in epileptogenesis.
Insulin resistance (IR) is the main feature of type 2 diabetes mellitus. Furthermore, viral infection can aggravate the abnormal glucose metabolism in diabetic patients. GABBR1 can maintain normal glucose homeostasis, bu...Insulin resistance (IR) is the main feature of type 2 diabetes mellitus. Furthermore, viral infection can aggravate the abnormal glucose metabolism in diabetic patients. GABBR1 can maintain normal glucose homeostasis, but its specific role in diabetes is not clear. We investigated the function of the GABBR1/miR-19b-3p/WNT2B axis and . miR-19b-3p and GABBR1 were overexpressed or knocked down in AML12 cells. Subsequently, these cells were treated with palmitic acid (PA) to induce damage or poly I : C to mimic viral infection. The degree of AML12 cell damage was assessed using the CCK-8 assay; inflammation levels were measured using ELISA; and IR indexes were determined using the Immunofluorescence kit and Western blot assay. The diabetic mice model was established to evaluate liver injury and IR. PA and poly I : C can reduce the activity of AML12 cells, increase apoptosis and inflammatory factor contents, weaken the ability of glucose uptake and consumption, enhance the production capacity, and reduce the level of GLUT4. GABBR1 mediates the targeted regulation of WNT2B by miR-19b-3p. PA and poly I : C also increased ALT, AST, inflammatory factors and miR-19b-3p levels, and decreased GABBR1 and WNT2B expression of mice. Liver cells showed swelling and many spherical lipid droplets. After miR-19b-3p knockdown and GABBR1 overexpression, the degree of liver injury and IR in AML12 cells and mice were alleviated. GABBR1 regulates miR-19b-3p/WNT2B axis to reduce liver injury, IR and inflammatory response, and improve the comorbidity of diabetes and viral infection. This pathway represents a potential therapeutic target for mitigating the comorbidity of diabetes and viral infection.
Cell cycle arrest in dermal fibroblasts is a critical biological process essential for maintaining skin homeostasis and serves as a central mechanism driving various skin pathologies. This review systematically summarize...Cell cycle arrest in dermal fibroblasts is a critical biological process essential for maintaining skin homeostasis and serves as a central mechanism driving various skin pathologies. This review systematically summarizes the endogenous and exogenous factors triggering cell cycle arrest in dermal fibroblasts and their underlying molecular mechanisms, with a particular focus on the roles of key signaling pathways such as p53, TGF-β/Smad, and Wnt/β-catenin. Additionally, the dual effects of cell cycle arrest on the skin are discussed: transient arrest facilitates DNA damage repair and tissue regeneration, whereas prolonged arrest leads to cellular senescence, chronic inflammation, collagen degradation, and fibrosis. Advances in chemical compounds modulating cell cycle arrest are also highlighted, including potential therapeutic strategies for promoting or relieving cell cycle arrest. This review provides new insights into skin regenerative medicine and anti-aging therapies while identifying critical scientific questions for future research.
Triple-negative breast cancer (TNBC) poses challenges in treatment due to its inherent biological characteristics. Endoplasmic reticulum stress (ERS) has been associated with the development of TNBC. Hence, identifying E...Triple-negative breast cancer (TNBC) poses challenges in treatment due to its inherent biological characteristics. Endoplasmic reticulum stress (ERS) has been associated with the development of TNBC. Hence, identifying ERS-related prognostic biomarkers is crucial for the early diagnosis and treatment of TNBC. In this study, we retrieved gene expression profiles from TNBC patients using The Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) between TNBC tumor and normal tissues were identified using limma package. Using differential expression analysis, we identified 46 ERS-related DEGs. Through univariate Cox, LASSO, and multivariate COX regression analyses, we constructed a prognostic model consisting of 8 genes (IGFBP1, CFTR, THBS4, CREBRF, CLU, HDGF, DERL3, NCCRP1). This model demonstrated robust prognostic accuracy in TNBC patients, validated by the METABRIC dataset. Among the 8 prognostic genes, NCCRP1 showed the highest expression increase in BT-20 and MDA-MB-468 cells. Functional assays further revealed that NCCRP1 significantly promoted proliferation, migration, and invasion, while suppressing apoptosis and ERS in these TNBC cell lines. Our study highlights a strong association between ERS-related genes and the prognosis of TNBC patients. Moreover, we demonstrated that NCCRP1 exerts oncogenic effects in TNBC cells. It provides new insights and possible treatment targets for TNBC.
Hepatocellular carcinoma (HCC) is characterized by high metastatic potential and poor prognosis. Ring finger protein 220 (RNF220) has been implicated in tumorigenesis across various cancers; however, its role and associa...Hepatocellular carcinoma (HCC) is characterized by high metastatic potential and poor prognosis. Ring finger protein 220 (RNF220) has been implicated in tumorigenesis across various cancers; however, its role and associated regulatory mechanisms in HCC remain unclear. In this study, analysis of The Cancer Genome Atlas (TCGA) database revealed that RNF220 expression was significantly elevated in liver hepatocellular carcinoma (LIHC) tissues and was associated with poor prognosis. Further experiments confirmed the upregulation of RNF220 mRNA and protein in HCC tissues. Functional assays demonstrated that RNF220 overexpression promoted cell proliferation, migration and stemness, whereas RNF220 knockdown suppressed these processes in HCC cells. Mechanistically, RNF220 enhanced ubiquitin-specific protease 22 (USP22) expression, leading to activation of the protein kinase B (Akt) pathway. Furthermore, the knockdown of RNF220 inhibited HCC progression, an effect that could be reversed by SC79 (an Akt activator), an Akt activator. In vivo experiments further confirmed that RNF220 aggravated tumor growth and metastasis. In summary, these findings indicate that RNF220 promotes HCC progression by regulating USP22 and activating the Akt pathway, suggesting that RNF220 may serve as a potential biomarker and therapeutic target for HCC.
The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are all implicated in tumor progression. This study investigat...The transforming growth factor-beta (TGF-β)/SMAD signaling pathway, mitogen-activated protein kinase (MAPK) signaling cascade, and dopamine receptor activity are all implicated in tumor progression. This study investigates molecular interactions among these pathways, identifying MAPK proteins that bridge SMAD and dopamine signaling in the context of breast cancer pathogenesis. A cohort of 405 breast cancer patients was categorized into molecular subtypes: luminal A ( = 130), luminal B HER2-negative ( = 100), luminal B HER2-positive ( = 96), non-luminal HER2-positive ( = 36), and triple-negative breast cancer (TNBC; = 43). Transcriptomic profiling using microarrays and bioinformatics-based network analysis revealed differentially expressed genes across subtypes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate 11 key transcripts, and protein expression was quantified by enzyme-linked immunosorbent assay (ELISA). MicroRNA (miRNA) regulatory interactions were analyzed to assess post-transcriptional modulation. Among 167 differentially expressed genes, 14 were consistently altered across all subtypes. These included cell division cycle 42 (), KRAS proto-oncogene, GTPase (), and transforming growth factor beta 1 (), which were upregulated, as well as fibroblast growth factor 2 (), fibroblast growth factor 7 (), and insulin-like growth factor 1 ), which were downregulated. miRNA analysis revealed miR-221, miR-222, and miR-16-5p as regulators of these pathways. ELISA confirmed reduced KIT, IGF1, and FGF family proteins in tumor tissues, with KRAS significantly upregulated. Protein interaction analysis highlighted key hubs linking MAPK, SMAD, and dopamine signaling. This study elucidates crucial molecular intersections between MAPK, SMAD, and dopamine pathways, identifying potential biomarkers and therapeutic targets for breast cancer.
Epithelial carcinoma cells require penetration of the basement membrane (BM) to metastasize. The BM is a thin layer of extracellular matrix beneath epithelial and endothelial tissues. It acts as a structural barrier, pre...Epithelial carcinoma cells require penetration of the basement membrane (BM) to metastasize. The BM is a thin layer of extracellular matrix beneath epithelial and endothelial tissues. It acts as a structural barrier, preventing cancer cells from invading and undergoing endocytosis and exocytosis. Thus, understanding the relationship between the BM and tumor immunity can lead to new strategies for halting cancer progression and metastasis. Gene expression data of 33 cancers were obtained from the Cancer Genome Atlas database. The study analyzed the correlation between BM regulatory genes, copy number variations, immune-related genes, and tumor immune dysfunction rejection (TIDE). Immunohistochemical methods were used to analyze the expression of regulatory genes. And the BM score was calculated using single-sample gene set enrichment analysis. Single-cell transcriptional sequencing determined the activation status of the BM in the tumor microenvironment. The expression of BM-related genes (BMGs) exhibited significant heterogeneity across different cancer types. Most genes were up-regulated in tumor tissues. Major single nucleotide polymorphisms of BMGs included missense mutations, while major copy number variations were heterozygous deletion and heterozygous amplification. Additionally, the expressions of immune checkpoint molecules CD276, NRP1, and C10orf54 showed positive correlations with BMS. Numerous tumors displayed a significant positive correlation between BMS and TIDE scores. We demonstrate that BM regulatory genes undergo alterations specific to different cancer types, which are associated with the expression of immune checkpoints and immune dysfunction. This indicates that BM remodeling plays an active role in modulating immune resistance, rather than being a passive structural alteration.