Molecular Carcinogenesis最新文献_第7页

Integrating Multi-Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk. 整合多指标数据，揭示前列腺组织 DNA 甲基化生物标记物和前列腺癌风险靶基因。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-14 DOI: 10.1002/mc.23828

Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu

{"title":"Integrating Multi-Omics Data to Uncover Prostate Tissue DNA Methylation Biomarkers and Target Genes for Prostate Cancer Risk.","authors":"Shuai Liu, Jingjing Zhu, Dylan Green, Hua Zhong, Quan Long, Chong Wu, Liang Wang, Youping Deng, Lang Wu","doi":"10.1002/mc.23828","DOIUrl":"10.1002/mc.23828","url":null,"abstract":"Previous studies have indicated that specific CpG sites may be linked to the risk of prostate cancer (PCa) by regulating the expression of PCa target genes. However, most existing studies aim to identify DNA methylation (DNAm) biomarkers through blood tissue genetic instruments, which impedes the identification of relevant biomarkers in prostate tissue. To identify PCa risk-associated CpG sites in prostate tissue, we established genetic prediction models of DNAm levels using data from normal prostate samples in the GTEx (N = 108) and assessed associations between genetically predicted DNAm in prostate and PCa risk by studying 122,188 cases and 604,640 controls. We observed significant associations for 3879 CpG sites, including 926 at novel genomic loci. Among them, DNAm levels of 80 CpG sites located at novel loci are significantly associated with expression levels of 45 neighboring genes in normal prostate tissue. Of these genes, 11 further exhibit significant associations with PCa risk for their predicted expression levels in prostate tissue. Intriguingly, a total of 31 CpG sites demonstrate consistent association patterns across the methylation-gene expression-PCa risk pathway. Our findings suggest that specific CpG sites may be related to PCa risk by modulating the expression of nearby target genes.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"83-90"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ZNF480 Accelerates Chemotherapy Resistance in Breast Cancer by Competing With TRIM28 and Stabilizing LSD1 to Upregulate the AKT-GSK3β-Snail Pathway. ZNF480通过与TRIM28竞争和稳定LSD1上调AKT-GSK3β-Snail通路加速乳腺癌的化疗耐药性

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-11-06 DOI: 10.1002/mc.23837

Xiaowen Ma, Yufeng Jiang, Hangqi Zhao, Yusong Qiu, Zhijian Liu, Xiupeng Zhang, Mingwei Fan, Yong Zhang, Yue Zhang

{"title":"ZNF480 Accelerates Chemotherapy Resistance in Breast Cancer by Competing With TRIM28 and Stabilizing LSD1 to Upregulate the AKT-GSK3β-Snail Pathway.","authors":"Xiaowen Ma, Yufeng Jiang, Hangqi Zhao, Yusong Qiu, Zhijian Liu, Xiupeng Zhang, Mingwei Fan, Yong Zhang, Yue Zhang","doi":"10.1002/mc.23837","DOIUrl":"10.1002/mc.23837","url":null,"abstract":"Zinc finger protein 480 (ZNF480) may interact with lysine-specific demethylase 1 (LSD1), which is highly expressed in many malignant tumors; however, ZNF480 expression has not previously been investigated in breast cancer. Therefore, we explored the expression and molecular mechanisms of ZNF480 in breast cancer. According to public databases and immunohistochemical staining analysis, ZNF480 is highly expressed in the tissue of patients with breast cancer, and ZNF480 expression is positively correlated with advanced TNM stage (p = 0.036), lymph node metastasis (p = 0.012), and poor prognosis (p = 0.005). ZNF480 overexpression enhances breast cancer cell proliferation, migration, and stemness by activating AKT-GSK3β-Snail signaling both in vitro and in vivo. Moreover, ZNF480 binds to LSD1 through its KRAB domain, thereby activating AKT signaling. Mass spectrometry and co-immunoprecipitation revealed that ZNF480 abrogates ubiquitination degradation and subsequently stabilizes LSD1 through competitive binding with TRIM28. Ipragliflozin was identified as a small-molecule inhibitor of ZNF480 and LSD1 interaction that may block breast cancer progression. Moreover, ZNF480 expression was significantly higher in treatment-resistant patients than in treatment-sensitive patients. Thus, ipragliflozin may neutralize neoadjuvant chemotherapy resistance induced by ZNF480 overexpression. Overall, elevated ZNF480 expression is positively associated with poor patient outcomes. Mechanistically, ZNF480 accelerates proliferation and neoadjuvant chemotherapy resistance in breast cancer cells via the AKT-GSK3β-Snail pathway by interacting with and stabilizing LSD1 in a competitive manner within TRIM28. This research has implications for developing targeted drugs against chemotherapy resistance in breast cancer.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"192-208"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functional Analysis of BARD1 Missense Variants on Homology-Directed Repair in Ovarian and Breast Cancers. BARD1错义变异对卵巢癌和乳腺癌同源定向修复的功能分析

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-10 DOI: 10.1002/mc.23829

Wenjing Li, Guansheng Chen, Yongjun Wang, Yuening Jiang, Nanlin Wu, Mingjie Hu, Taju Wu, Wei Yue

{"title":"Functional Analysis of BARD1 Missense Variants on Homology-Directed Repair in Ovarian and Breast Cancers.","authors":"Wenjing Li, Guansheng Chen, Yongjun Wang, Yuening Jiang, Nanlin Wu, Mingjie Hu, Taju Wu, Wei Yue","doi":"10.1002/mc.23829","DOIUrl":"10.1002/mc.23829","url":null,"abstract":"Women with germline BRCA1 mutations face an increased risk of developing breast and ovarian cancers. BARD1 (BRCA1 associated RING domain 1) is an essential heterodimeric partner of BRCA1, and mutations in BARD1 are also associated with these cancers. While BARD1 mutations are recognized for their cancer susceptibility, the exact roles of numerous BARD1 missense mutations remain unclear. In this study, we conducted functional assays to assess the homology-directed DNA repair (HDR) activity of all BARD1 missense substitutions identified in 55 breast and ovarian cancer samples, using the real-world data from the COSMIC and cBioPortal databases. Seven BARD1 variants (V85M, P187A, G491R, R565C, P669L, T719R, and Q730L) were confirmed to impair DNA damage repair. Furthermore, cells harboring these BARD1 variants exhibited increased sensitivity to the chemotherapeutic drugs, cisplatin, and olaparib, compared to cells expressing wild-type BARD1. These findings collectively suggest that these seven missense BARD1 variants are likely pathogenic and may respond well to cisplatin-olaparib combination therapy. This study not only enhances our understanding of BARD1's role in DNA damage repair but also offers valuable insights into predicting therapy responses in patients with specific BARD1 missense mutations.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"91-107"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Delta-Like Homolog 2 Facilitates Malignancy of Hepatocellular Carcinoma via Activating EGFR/PKM2 Signaling Pathway. Delta-Like同源物2通过激活表皮生长因子受体/PKM2信号通路促进肝细胞癌恶变

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-28 DOI: 10.1002/mc.23836

Xiangye Liu, Tingting Li, Yuting Wang, Xiaoge Gao, Feitong Wang, Yang Chen, Kaisheng Wang, Weiming Luo, Fanyun Kong, Yanbo Kou, Hongjuan You, Delong Kong, Qing Zhang, Renxian Tang

{"title":"Delta-Like Homolog 2 Facilitates Malignancy of Hepatocellular Carcinoma via Activating EGFR/PKM2 Signaling Pathway.","authors":"Xiangye Liu, Tingting Li, Yuting Wang, Xiaoge Gao, Feitong Wang, Yang Chen, Kaisheng Wang, Weiming Luo, Fanyun Kong, Yanbo Kou, Hongjuan You, Delong Kong, Qing Zhang, Renxian Tang","doi":"10.1002/mc.23836","DOIUrl":"10.1002/mc.23836","url":null,"abstract":"Delta-like homolog 2 (DLK2) plays a crucial role in adipogenesis, chondrogenic differentiation, and the progression of certain cancers. However, the key roles of DLK2 underlying the progression of hepatocellular carcinoma (HCC) remain ambiguous. In the current study, we demonstrate that DLK2 is upregulated in HCC, significantly correlated with clinicopathological variables and serves as an independent diagnostic marker. Functional assays reveal that DLK2 facilitates malignant progression of HCC in vitro and in vivo models. Mechanistically, DLK2 binds to EGFR resulting in its auto-phosphorylation, which activates NF-κB pathway leading to P65-dependent transcriptional upregulation of PKM2. Furthermore, that elevates both enzyme-dependent and -independent activities of PKM2 contributing to cancer proliferation and metastasis. In summary, our findings demonstrate a novel pro-tumoral role and mechanism of DLK2 in the regulation of HCC malignant progression, suggesting its potential as a clinical diagnostic marker and therapeutic target.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"176-191"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FGFR2 in the Development and Progression of Cutaneous Squamous Cell Cancer. 表皮生长因子受体 2（FGFR2）在皮肤鳞状细胞癌的发生和发展中的作用

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-28 DOI: 10.1002/mc.23835

Ethan M Kallenberger, Alok Khandelwal, Priyatosh Nath, Shaun A Nguyen, John DiGiovanni, Cherie-Ann Nathan

{"title":"FGFR2 in the Development and Progression of Cutaneous Squamous Cell Cancer.","authors":"Ethan M Kallenberger, Alok Khandelwal, Priyatosh Nath, Shaun A Nguyen, John DiGiovanni, Cherie-Ann Nathan","doi":"10.1002/mc.23835","DOIUrl":"10.1002/mc.23835","url":null,"abstract":"Cutaneous squamous cell carcinoma (cSCC) is an increasingly common malignancy of the skin and the leading cause of death from skin cancer in adults over the age of 85. Fibroblast growth factor receptor 2 (FGFR2) has been identified as an important effector of signaling pathways that lead to the growth and development of cSCC. In recent years, there have been numerous studies evaluating the role FGFR2 plays in multiple cancers, its contribution to resistance to anticancer therapy, and new drugs that may be used to inhibit FGFR2. This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: (1) to highlight our current knowledge of the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; (2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; (3) to describe how FGFR2 contributes to more invasive disease; (4) to describe its immunosuppressive effects in skin; and (5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"5-13"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8⁺ T Cells in Triple-Negative Breast Cancer. FOS 介导的 PLCB1 在三阴性乳腺癌中诱导放射抗性并削弱 CD8+ T 细胞的抗肿瘤作用

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-25 DOI: 10.1002/mc.23834

Yuxian Shu, Jun Lan, Huijing Luo, Huiying Fu, Xuhuang Xiao, Liping Yang

{"title":"FOS-Mediated PLCB1 Induces Radioresistance and Weakens the Antitumor Effects of CD8+ T Cells in Triple-Negative Breast Cancer.","authors":"Yuxian Shu, Jun Lan, Huijing Luo, Huiying Fu, Xuhuang Xiao, Liping Yang","doi":"10.1002/mc.23834","DOIUrl":"10.1002/mc.23834","url":null,"abstract":"Radioresistance and immune evasion are interactive and crucial events leading to treatment failure and progression of human malignancies. This research studies the role of phospholipase C beta 1 (PLCB1) in these events in triple-negative breast cancer (TNBC) and the regulatory mechanism. PLCB1 was bioinformatically predicted as a dysregulated gene potentially linked to radioresistance in TNBC. Parental TNBC cell lines were exposed to fractionated radiation for 6 weeks. PLCB1 expression was decreased in the first 2 weeks but gradually increased from Week 3. PLCB1 knockdown increased the radiosensitivity of the cells, as manifested by a decreased half-inhibitory dose of irradiation, reduced cell proliferation, apoptosis resistance, mobility, and tumorigenesis in mice. The FOS transcription factor promoted PLCB1 transcription and activated the PI3K/AKT signaling. Knockdown of FOS similarly reduced radioresistance and T cells-mediated immune evasion. However, the radiosensitivity of TNBC cells and the antitumor effects of CD8+ T cells could be affected by a PI3K/AKT activator or by the PLCB1 upregulation. The PLCB1 or FOS knockdown also suppressed radioresistance and tumorigenesis of the TNBC cells in mice. In conclusion, FOS-mediated PLCB1 induces radioresistance and weakens the antitumor effects of CD8+ T cells in TNBC by activating the PI3K/AKT signaling pathway.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"162-175"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ALKBH5-Mediated m⁶A Modification of XBP1 Facilitates NSCLC Progression Through the IL-6-JAK-STAT3 Pathway. ALKBH5 介导的 XBP1 m6A 修饰通过 IL-6-JAK-STAT3 通路促进 NSCLC 进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-10 DOI: 10.1002/mc.23826

Hengxing Liang, Chunmin Zhang, Minxin Hu, Fang Hu, Saihui Wang, Wei Wei, Wen Hu

{"title":"ALKBH5-Mediated m6A Modification of XBP1 Facilitates NSCLC Progression Through the IL-6-JAK-STAT3 Pathway.","authors":"Hengxing Liang, Chunmin Zhang, Minxin Hu, Fang Hu, Saihui Wang, Wei Wei, Wen Hu","doi":"10.1002/mc.23826","DOIUrl":"10.1002/mc.23826","url":null,"abstract":"The X-box-binding protein 1 (XBP1) is an important transcription factor during endoplasmic reticulum stress response, which was reported as an oncogene in non-small cell lung cancer (NSCLC) tumorigenesis and development. However, the regulatory mechanism of XBP1 expression in NSCLC progression was less reported. N6-methyladenosine (m6A) RNA modification is an emerging epigenetic regulatory mechanism for gene expression. This study aimed to investigate the regulatory role of the m6A modification in XBP1 expression in NSCLC. We identified XBP1 as a downstream target of ALKBH5-mediated m6A modification in A549 and PC9 cells. Knockdown of ALKBH5 increased the m6A modification and the stability of XBP1 mRNA, while overexpression of ALKBH5 had the opposite effect. Furthermore, IGF2BP3 was confirmed to be a reader of XBP1 m6A methylation and to enhance the stability of XBP1 mRNA. Additionally, IGF2BP3 knockdown significantly reversed the increase in XBP1 stability mediated by ALKBH5 depletion. In vivo and in vitro experiments demonstrated that ALKBH5/IGF2BP3 promotes the proliferation, migration, and invasion of NSCLC cells by upregulating XBP1 expression. In addition, we also showed that XBP1 promoted NSCLC cell proliferation, migration, and invasion by activating IL-6-JAK-STAT3 signaling. Our research suggested that ALKBH5-mediated m6A modification of XBP1 facilitates NSCLC progression through the IL-6-JAK-STAT3 pathway.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"57-71"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hepatitis B Virus X Protein Contributes to Hepatocellular Carcinoma via Upregulation of KIAA1429 Methyltransferase and mRNA m6A Hypermethylation of HSPG2/Perlecan. 乙型肝炎病毒 X 蛋白通过上调 KIAA1429 甲基转移酶和 mRNA m6A 对 HSPG2/Perlecan 的超甲基化作用诱发肝细胞癌

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-16 DOI: 10.1002/mc.23830

Enakshi Sivasudhan, Jingxian Zhou, Jiongming Ma, Yuanyuan Wang, Siying Liu, Faez Iqbal Khan, Zhiliang Lu, Jia Meng, Neil Blake, Rong Rong

{"title":"Hepatitis B Virus X Protein Contributes to Hepatocellular Carcinoma via Upregulation of KIAA1429 Methyltransferase and mRNA m6A Hypermethylation of HSPG2/Perlecan.","authors":"Enakshi Sivasudhan, Jingxian Zhou, Jiongming Ma, Yuanyuan Wang, Siying Liu, Faez Iqbal Khan, Zhiliang Lu, Jia Meng, Neil Blake, Rong Rong","doi":"10.1002/mc.23830","DOIUrl":"10.1002/mc.23830","url":null,"abstract":"Chronic hepatitis B virus (HBV) remains to be the most common risk factor of hepatocellular carcinoma (HCC). While previous work has primarily focussed on understanding the direct and indirect mechanisms of Hepatitis B virus X protein (HBx)-mediated hepatocarcinogenesis, from genetic and epigenetic perspectives, its influence on RNA modification mediated onset of liver malignancies is less well understood. This study explored the role of HBV-encoded HBx in altering the m6A methylome profile and its implications on the pathogenesis of HCC. We established HBx-expressing stable HCC cell lines, Huh7-HBx and HepG2-HBx, and explored the transcriptomic and epitranscriptomic profiles by RNA-seq and MeRIP-seq, respectively. Preliminary results suggest that HBx promotes liver cell proliferation, migration, survival and overall m6A methylation in HCC cells and is involved in modulating the extracellular matrix. We show that HBx mediates liver cell transformation by upregulating KIAA1429 methyltransferase. HBx also drives the expression and hypermethylation of the extracellular matrix protein HSPG2/Perlecan and promotes tumourigenesis. Furthermore, we observed a potential interaction between KIAA1429 and HSPG2 in HCC liver cancer cells and demands further investigation.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"108-125"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

EXPRESSION OF CONCERN: Combination Cisplatin and Sulforaphane Treatment Reduces Proliferation, Invasion, and Tumor Formation in Epidermal Squamous Cell Carcinoma. 表达关切：顺铂和红景天联合治疗可减少表皮鳞状细胞癌的增殖、侵袭和肿瘤形成。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI: 10.1002/mc.23858

引用次数: 0

Sohlh2 Promotes the Progression of Hepatocellular Carcinoma via TGM2-Mediated Autophagy. Sohlh2 通过 TGM2 介导的自噬促进肝细胞癌的进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-01-01 Epub Date: 2024-10-22 DOI: 10.1002/mc.23832

Xuyue Liu, Ruihong Zhang, Lanlan Liu, Sujuan Zhi, Xiaoning Feng, Ying Shen, Liyan Wang, Qi Zhang, Yanru Chen, Jing Hao

{"title":"Sohlh2 Promotes the Progression of Hepatocellular Carcinoma via TGM2-Mediated Autophagy.","authors":"Xuyue Liu, Ruihong Zhang, Lanlan Liu, Sujuan Zhi, Xiaoning Feng, Ying Shen, Liyan Wang, Qi Zhang, Yanru Chen, Jing Hao","doi":"10.1002/mc.23832","DOIUrl":"10.1002/mc.23832","url":null,"abstract":"Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for 85% of liver cancer-related deaths. Autophagy controls HCC cell growth, invasion, metastasis, drug resistance, and stemness. Spermatogenesis and oogenesis basic helix-loop-helix transcription factor 2 (Sohlh2) can bind to the E-boxes in the promoter regions of target genes, which are involved in multiple neoplasms. In this study, Sohlh2 was highly expressed in HCC tissues and was related to poor prognosis. Moreover, Sohlh2 overexpression promoted the proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. However, Sohlh2 silencing inhibited proliferation, migration, invasion, and metastasis of HCC cells in vivo and in vitro. Mechanistically, Sohlh2 could bind to the promoter of TGM2 and enhance its transcriptional activity, thereby enhancing the autophagy of HCC cells. Furthermore, Sohlh2 protein levels were positively associated with TGM2 expression in HCC tissues. Taken together, these results demonstrate that Sohlh2 can promote HCC progression via TGM2-mediated autophagy, implying that Sohlh2 is a promising candidate for HCC treatment.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"138-151"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0