Molecular Carcinogenesis最新文献

RNF7-Mediated ROS Targets Malignant Phenotype and Radiotherapy Sensitivity in Glioma With Different IDH1 Genotypes. rnf7介导的ROS靶向不同IDH1基因型胶质瘤的恶性表型和放疗敏感性

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-09 DOI: 10.1002/mc.23876

Yiran Tao, Zimin Shi, Xianyin Liang, Yuqian Zheng, Lirui Dai, Xiang Li, Zian Li, Wulong Liang, Gaojie Bai, Hao Li, Yuan Lyu, Junqi Li, Tao Zhang, Weihua Hu, Shaolong Zhou, Qiao Shan, Xudong Fu, Xinjun Wang

{"title":"RNF7-Mediated ROS Targets Malignant Phenotype and Radiotherapy Sensitivity in Glioma With Different IDH1 Genotypes.","authors":"Yiran Tao, Zimin Shi, Xianyin Liang, Yuqian Zheng, Lirui Dai, Xiang Li, Zian Li, Wulong Liang, Gaojie Bai, Hao Li, Yuan Lyu, Junqi Li, Tao Zhang, Weihua Hu, Shaolong Zhou, Qiao Shan, Xudong Fu, Xinjun Wang","doi":"10.1002/mc.23876","DOIUrl":"10.1002/mc.23876","url":null,"abstract":"RNF7 (Ring Finger Protein 7) is a key component of CRLs (Cullin-RING-type E3 ubiquitin ligases) and has been found to possess intrinsic anti-ROS capabilities. Aberrant expression of RNF7 has been observed in various tumor types and is known to significantly influence tumor initiation and progression. However, the specific role of RNF7 in glioblastoma remains unclear. IDH (isocitrate dehydrogenase) mutations, which induce metabolic reprogramming and result in notable heterogeneity among glioma with different IDH genotypes. Through analysis of public glioma databases, we identified a high expression of RNF7 in glioma and its correlation with patient prognosis. Moreover, we observed variations in RNF7 expression and its association with patient outcomes under different treatment modalities among different IDH genotypes. In this study, we demonstrated the critical role of RNF7 in the malignant phenotype of IDH1-mutant glioma and its contribution to radiation resistance. Subsequent functional enrichment analysis of RNF7 in glioma, coupled with validation through cellular experiments, confirmed its significant involvement in maintaining redox balance. Our findings suggest that RNF7 exerts a buffering effect against radiation-induced oxidative stress and counterbalances the redox stress induced by IDH1 mutation through its anti-ROS activity. Additionally, our follow-up investigations revealed that the upregulation of RNF7 after radiation exposure and in IDH1-mutant glioma cells is induced by ROS. Collectively, our study underscores the potential of RNF7 as a molecular biomarker in glioma. Elevated RNF7 expression often indicates a heightened metabolic resilience in glioma, leading to resistance against radiotherapy.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"652-667"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

VPS45 Contributes to the Progression of Hepatocellular Carcinoma by Triggering the Wnt/β-Catenin Signaling Pathway. VPS45通过触发Wnt/β-Catenin信号通路参与肝细胞癌的进展

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-21 DOI: 10.1002/mc.23884

Renhou Zhi, Qi Li, Huiqin Zhang, Fan Fan

{"title":"VPS45 Contributes to the Progression of Hepatocellular Carcinoma by Triggering the Wnt/β-Catenin Signaling Pathway.","authors":"Renhou Zhi, Qi Li, Huiqin Zhang, Fan Fan","doi":"10.1002/mc.23884","DOIUrl":"10.1002/mc.23884","url":null,"abstract":"Vacuolar protein sorting 45 (VPS45) has recently been implicated in the development of ovarian cancer and non-small cell lung cancer. However, its role in the onset and progression of hepatocellular carcinoma (HCC) remains unclear. This study aims to elucidate the function of VPS45 in HCC. Bioassays were conducted to assess the prognostic significance of VPS45 in HCC. Techniques such as western blotting and real-time quantitative polymerase chain reaction (qRT-PCR) were used to confirm the expression levels of VPS45 in HCC tissues and cell lines, as well as to evaluate the expression of downstream effectors in its potential tumorigenic pathways. The impact of VPS45 on HCC cell invasion, proliferation, and migration was assessed using the Cell Counting Kit-8 (CCK-8), wound healing, and transwell assays. Furthermore, the effect of VPS45 on HCC tumorigenesis in vivo was evaluated through subcutaneous tumor formation assays in BALB/c nude mice. VPS45 is markedly overexpressed in both HCC tissues and cell lines. Its expression escalates with advancing tumor grade and clinical stage, and high VPS45 levels are indicative of poor prognosis. In vitro experiments revealed that VPS45 overexpression significantly boosts HCC cell proliferation, migration, and invasion. Conversely, VPS45 knockdown hindered HCC progression in vivo. Investigation into pathway protein expression suggests that VPS45 facilitates HCC progression through its involvement in the Wnt/β-catenin signaling pathway. The overexpression of VPS45 contributes to the development of malignant phenotypes in HCC cells, resulting in a poor prognosis. Targeting VPS45 may offer a viable therapeutic strategy for managing HCC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"744-755"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma. FKBP脯氨酸异构酶11：食管癌中与SRSF1相互作用的新癌基因

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-08 DOI: 10.1002/mc.23877

Zheng Ding, Zhichao Hou, Tangjuan Zhang, Peng Wang, Xue Pan, Xiangnan Li, Song Zhao

{"title":"FKBP Prolyl Isomerase 11: A Novel Oncogene Interacting With SRSF1 in Esophageal Squamous Cell Carcinoma.","authors":"Zheng Ding, Zhichao Hou, Tangjuan Zhang, Peng Wang, Xue Pan, Xiangnan Li, Song Zhao","doi":"10.1002/mc.23877","DOIUrl":"10.1002/mc.23877","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is one of the main subtypes of esophageal carcinoma with high morbidity. This study aimed to explore the role of FKBP prolyl isomerase 11 (FKBP11) in ESCC and investigate the underlying mechanism. FKBP11 levels in ESCC tumor tissues and cell lines were measured. Cell function assays were conducted to evaluate the role of FKBP11 in ESCC cells. The xenograft mouse model was established to validate the effect of FKBP11 on ESCC tumorigenesis in vivo. The co-immunoprecipitation assay was performed to determine the FKBP11-interacting proteins. Obvious upregulations in FKBP11 expression were found in ESCC tumor tissues and cell lines. In vitro, FKBP11 knockdown weakened cell proliferation, migration, and invasion capacities and reinforced cell apoptosis in ESCC cells. In vivo, FKBP11 knockdown slowed ESCC tumorigenesis. The following mechanism investigation determined serine and arginine-rich splicing factor 1 (SRSF1) as the FKBP11-interacting protein in ESCC cells. FKBP11 directly bound to SRSF1 and FKBP11 knockdown decreased SRSF1 mRNA level. SRSF1 overexpression abrogated the inhibitory effect of FKBP11 knockdown on the proliferation and migration of ESCC cells. KBP11 functions as an oncogene in ESCC by targeting SRSF1.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"638-651"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952056","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

LncRNA FGD5-AS1 Facilitates Hepatocellular Carcinoma Cell Stemness by Enhancing PKD1 mRNA Stability Through Binding With MSI2. LncRNA FGD5-AS1通过与MSI2结合增强PKD1 mRNA稳定性，促进肝癌细胞的干细胞性

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI: 10.1002/mc.23873

Chenkun He, Rongrong Liu, Tianli Zhou

{"title":"LncRNA FGD5-AS1 Facilitates Hepatocellular Carcinoma Cell Stemness by Enhancing PKD1 mRNA Stability Through Binding With MSI2.","authors":"Chenkun He, Rongrong Liu, Tianli Zhou","doi":"10.1002/mc.23873","DOIUrl":"10.1002/mc.23873","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major global health concern that accounts for more than 80% of all primary hepatic carcinomas. The long noncoding RNA FGD5 antisense RNA 1 (FGD5-AS1) has been linked to HCC cell stemness and proliferation. However, the exact function of FGD5-AS1 in HCC remains unclear. Cell viability and proliferation were examined using the CCK8 and colony formation assays, respectively. Cell stemness was examined using a sphere formation assay. To investigate the relation between Musashi 2 (MSI2) and FGD5-AS1 (or protein kinase D1 [PKD1]), RNA immunoprecipitation and RNA pull-down assays were used. Furthermore, a xenograft mouse model was established to evaluate the function of FGD5-AS1 in vivo. FGD5-AS1, MSI2, and PKD1 were upregulated in the HCC tissues. FGD5-AS1 knockdown significantly inhibited the viability, proliferation, and stemness of HCC cells and decreased the expression of MSI2, PKD1, octamer-binding transcription factor 4, SOX2, NANOG, and Prominin-1 in HCC cells. Mechanistically, FGD5-AS1 increased PKD1 mRNA stability by upregulating MSI2 expression. Both MSI2 and PKD1 ameliorated sh-FGD5-AS1's inhibition of HCC cell viability, proliferation, and stemness. Furthermore, FGD5-AS1 silencing inhibited HCC tumor growth and stemness in vivo. FGD5-AS1 promotes the stemness of HCC cells by activating the MSI2/PKD1 axis. Our study provides a new theoretical foundation for the development of novel HCC treatments.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"680-690"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971483","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

β-Elemene Inhibits Adrenocortical Carcinoma Cell Proliferation and Migration, and Induces Apoptosis by Up-Regulating miR-486-3p/Targeting NPTX1 Axis. β-榄香烯通过上调miR-486-3p/靶向NPTX1轴抑制肾上腺皮质癌细胞增殖和迁移，诱导细胞凋亡。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI: 10.1002/mc.23879

Yan Lin, Tailin Guo, Lishuang Che, Jieqiong Dong, Ting Yu, Chaiming Zeng, Ziyu Wu

{"title":"β-Elemene Inhibits Adrenocortical Carcinoma Cell Proliferation and Migration, and Induces Apoptosis by Up-Regulating miR-486-3p/Targeting NPTX1 Axis.","authors":"Yan Lin, Tailin Guo, Lishuang Che, Jieqiong Dong, Ting Yu, Chaiming Zeng, Ziyu Wu","doi":"10.1002/mc.23879","DOIUrl":"10.1002/mc.23879","url":null,"abstract":"β-elemene has a variety of anti-inflammatory, antioxidant, and antitumor effects. Currently, the influence of β-elemene on adrenocortical carcinoma (ACC) malignant progression and action mechanism remains unclear. This research aims to explore the influence and action mechanism of β-elemene on ACC progression. The impacts of β-elemene on ACC cell viability, proliferation, migration, and apoptosis were investigated through CCK-8 assay, clone formation assay, Transwell experiment, Wound healing assay, and flow cytometry. The miR-486-3p expression was analyzed utilizing RT-qPCR. According to different databases, neuronal pentraxin 1 (NPTX1) is the predicted downstream target gene of miR-486-3p. Western blot and RT-qPCR were utilized to examine NPTX1 expression. Silencing miR-486-3p or Overexpression NPTX1 in ACC cells further explored whether β-elemene affects ACC cells by regulating miR-486-3p/NPTX1. Finally, a subcutaneous graft tumor model was constructed to investigate how β-elemene may impact tumor growth in vivo. β-elemene decreased the cell viability, hindered cell proliferation and migration capacity, and induced apoptosis of ACC cells. miR-486-3p level in ACC cells was notably reduced in comparison to normal cells, but treatment with β-elemene markedly increased miR-486-3p expression. Additionally, ACC cells showed high level of NPTX1, while miR-486-3p targeted negative regulation of NPTX1. Overexpression miR-486-3p hindered the malignant progression of ACC cells, whereas overexpression NPTX1 reversed the impact of overexpression miR-486-3p. Silencing miR-486-3p or overexpression NPTX1 both attenuated the suppressive influence of β-elemene on the malignant behavior of ACC cells. Additionally, tumor growth was suppressed and apoptosis was induced in tumor cells in vivo by β-elemene. In conclusion, β-elemene reduces ACC cell viability, hinders proliferation and migration, and induces apoptosis through the miR-486-3p/NPTX1 axis.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"691-702"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971634","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

HGF/c-Met Promotes Breast Cancer Tamoxifen Resistance Through the EZH2/HOTAIR-miR-141/200a Feedback Signaling Pathway.

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-24 DOI: 10.1002/mc.23878

Xiaofeng Lai, Yuan Zhang, Mengyang Li, Shentong Yu, Shuiliang Wang, Shenghang Zhang, Huimin Niu, Li Chen, Xiaopeng Lan, Jian Zhang, Suning Chen

引用次数: 0

LINC01305 and LAD1 Co-Regulate CTTN and N-WASP Phosphorylation, Mediating Cytoskeletal Reorganization to Promote ESCC Metastasis. LINC01305和LAD1共同调控CTTN和N-WASP磷酸化，介导细胞骨架重组促进ESCC转移。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-21 DOI: 10.1002/mc.23885

Hang Yang, Rong Xiong, Ruolan Zhang, Shan Sun, Yingjie Pan, Quanneng Zhao, Jun Bie, Yi Luo, Guiqin Song, Kang Liu

{"title":"LINC01305 and LAD1 Co-Regulate CTTN and N-WASP Phosphorylation, Mediating Cytoskeletal Reorganization to Promote ESCC Metastasis.","authors":"Hang Yang, Rong Xiong, Ruolan Zhang, Shan Sun, Yingjie Pan, Quanneng Zhao, Jun Bie, Yi Luo, Guiqin Song, Kang Liu","doi":"10.1002/mc.23885","DOIUrl":"10.1002/mc.23885","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is prone to metastasis and is a leading cause of mortality. The cytoskeleton is closely related to cell morphology and movement; however, little research has been conducted on ESCC metastasis. In this study, we found that the anchoring filament protein ladinin 1 (LAD1) specifically binds to LINC01305 for co-regulating the level of modulating cortactin proteins (CTTN) and neuronal Wiskott-Aldrich syndrome protein (N-WASP) phosphorylation, which mediates cytoskeletal reorganization and affects the metastasis of ESCC cells. Additionally, LINC01305 and LAD1 jointly promoted the epithelial-mesenchymal transition (EMT) process by activating the phosphoinositide-3-kinase-protein kinase B (PI3K/AKT) signaling pathway. Moreover, LINC01305 and LAD1 were related to the late clinical stage and lymph node metastasis of ESCC. Our study demonstrated that LINC01305 and LAD1 are major determinants of ESCC dissemination and revealed a novel molecular mechanism of cytoskeletal reorganization that controls ESCC metastasis. Trial Registration: N/A.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"756-768"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Transcription Factor ATF2 Accelerates Clear Cell Renal Cell Carcinoma Progression Through Activating the PLEKHO1/NUS1 Pathway. 转录因子ATF2通过激活PLEKHO1/NUS1通路加速透明细胞肾细胞癌的进展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-08 DOI: 10.1002/mc.23868

Zheng Lu, Jinge Xu, Junyu Li

{"title":"The Transcription Factor ATF2 Accelerates Clear Cell Renal Cell Carcinoma Progression Through Activating the PLEKHO1/NUS1 Pathway.","authors":"Zheng Lu, Jinge Xu, Junyu Li","doi":"10.1002/mc.23868","DOIUrl":"10.1002/mc.23868","url":null,"abstract":"Clear cell renal cell carcinoma (ccRCC) is a common malignant cancer with high mortality rate. Activating transcription factor 2 (ATF2) and pleckstrin homology domain containing O1 (PLEKHO1) were reported to participate in numerous cancers. However, their roles and the detailed mechanisms in ccRCC development remain largely unknown. RT-qPCR and western blot were used to measure the levels of PLEKHO1, ATF2, and nuclear undecaprenyl pyrophosphate synthase 1 (NUS1). Cell proliferation, apoptosis, invasion, migration and stemness were evaluated using CCK-8 assay, flow cytometry, transwell invasion assay, wound-healing assay and sphere formation assay, respectively. Dual-luciferase reporter assay was conducted to verify the relationship between ATF2 and PLEKHO1. The interaction between PLEKHO1 and NUS1 was proved by Co-IP assay. Xenograft models were utilized to evaluate the tumorigenic capability of ccRCC cells upon PLEKHO1 knockdown. PLEKHO1, ATF2 and NUS1 expression were significantly elevated in ccRCC, and PLEKHO1 might be a prognosis biomarker for ccRCC. PLEKHO1 depletion significantly inhibited cell proliferation, invasion, migration, stemness, and induced cell apoptosis in ccRCC cells. ATF2 activated PLEKHO1 expression via transcription regulation, and PLEKHO1 overexpression could reverse the suppressive effects of ATF2 knockdown on the malignant behaviors of ccRCC cells. Moreover, PLEKHO1 directly bound to NUS1, and PLEKHO1 depletion markedly restrained ccRCC progression through targeting NUS1 in vitro and in vivo. Our findings suggested that ATF2 transcriptionally activated PLEKHO1 to promote the development of ccRCC via regulating NUS1 expression.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"617-628"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952061","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

TRIM36 Inhibits the Development of AOM/DSS-Induced Colitis-Associated Colorectal Cancer by Promoting the Ubiquitination and Degradation of GRB7. TRIM36通过促进GRB7的泛素化和降解抑制AOM/ dss诱导的结肠炎相关结直肠癌的发展。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-13 DOI: 10.1002/mc.23871

Ju Wu, Zhengbo Yang, Xi Chen, Shuangshuang Hou, Nanbo Li, Yaoyuan Chang, Jiajun Yin, Jian Xu

{"title":"TRIM36 Inhibits the Development of AOM/DSS-Induced Colitis-Associated Colorectal Cancer by Promoting the Ubiquitination and Degradation of GRB7.","authors":"Ju Wu, Zhengbo Yang, Xi Chen, Shuangshuang Hou, Nanbo Li, Yaoyuan Chang, Jiajun Yin, Jian Xu","doi":"10.1002/mc.23871","DOIUrl":"10.1002/mc.23871","url":null,"abstract":"Colorectal cancer (CRC) is among the most common cancer types for both sexes. Tripartite motif 36 (TRIM36) has been reported to be aberrantly expressed in several cancer types, suggesting its involvement in cancer progression. However, the role of TRIM36 in the colorectal carcinogenesis remain unknown. In our in vivo experiments, we investigated the role of TRIM36 in AOM/DSS-induced colitis-associated carcinogenesis using TRIM36-knockout (TRIM36 KO) mice. Subsequently, we overexpressed and knocked down TRIM36 expression in two CRC cell lines to further confirm the role of TRIM36 in vitro. The UALCAN database revealed a significant decrease in TRIM36 levels in CRC tissues, including colon adenocarcinoma and rectum adenocarcinoma. A significant correlation was observed between TRIM36 levels and the histological subtype, individual cancer stage, and nodal metastasis status. The downregulation of TRIM36 in CRC tissues was further confirmed using our own collected clinical specimens. Low expression of TRIM36 was found to be associated with unfavorable overall survival and recurrence-free survival in CRC. TRIM36 KO promoted inflammation, inhibited autophagy, and facilitated the development of AOM/DSS-induced CRC. TRIM36 overexpression inhibited proliferation, migration, and invasion, while activated autophagy in CRC cells. TRIM36 directly bound to and regulated the ubiquitination of GRB7 protein. The tumor-suppressive role of TRIM36 in CRC cells was mediated by GRB7. The TRIM36/GRB7 axis may represent a promising therapeutic target for the treatment of CRC.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"668-679"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971484","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

Computed Tomography-Based Radiomics and Genomics Analyses for Survival Prediction of Stage III Unresectable Non-Small Cell Lung Cancer Treated With Definitive Chemoradiotherapy and Immunotherapy. 基于计算机层析成像的放射组学和基因组学分析对III期不可切除的非小细胞肺癌进行确定性放化疗和免疫治疗的生存预测。

IF 3 2区医学

Molecular Carcinogenesis Pub Date : 2025-04-01 Epub Date: 2025-01-21 DOI: 10.1002/mc.23883

Yuxin Geng, Tianwen Yin, Yikun Li, Kaixing He, Bingwen Zou, Jinming Yu, Xiao Sun, Tao Zhang, Feifei Teng

{"title":"Computed Tomography-Based Radiomics and Genomics Analyses for Survival Prediction of Stage III Unresectable Non-Small Cell Lung Cancer Treated With Definitive Chemoradiotherapy and Immunotherapy.","authors":"Yuxin Geng, Tianwen Yin, Yikun Li, Kaixing He, Bingwen Zou, Jinming Yu, Xiao Sun, Tao Zhang, Feifei Teng","doi":"10.1002/mc.23883","DOIUrl":"10.1002/mc.23883","url":null,"abstract":"The standard therapy for locally unresectable advanced non-small cell lung cancer (NSCLC) is comprised of chemoradiotherapy (CRT) before immunotherapy (IO) consolidation. However, how to predict treatment outcomes and recognize patients that will benefit from IO remain unclear. This study aimed to identify prognostic biomarkers by integrating computed tomography (CT)-based radiomics and genomics. Specifically, our research involved 165 patients suffering from unresectable Stage III NSCLC. Cohort 1 (IO following CRT) was divided into D1 (n = 74), D2 (n = 32), and D3 (n = 26) sets, and the remaining 33 patients treated with CRT alone were grouped in D4. According to the CT images of primary tumor regions, radiomic features were analyzed through the least absolute shrinkage and selection operator (LASSO) regression. The Rad-score was figured out to forecast the progression-free survival (PFS). According to the Rad-score, patients were divided into high and low risk groups. Next-generation sequencing was implemented on peripheral blood and tumor tissue samples in the D3 and D4 cohorts. The maximum somatic allele frequency (MSAF) about circulating tumor DNA levels was assessed. Mismatch repair and switching/sucrose non-fermenting signaling pathways were significantly enriched in the low-risk group compared to the high-risk group (p < 0.05). Moreover, patients with MSAF ≥ 1% and those showing a decrease in MSAF after treatment significantly benefited from IO. This study developed a radiomics model predicting PFS after CRT and IO in Stage III NSCLC and constructed a radio-genomic map to identify underlying biomarkers, supplying valuable insights for cancer biology.","PeriodicalId":19003,"journal":{"name":"Molecular Carcinogenesis","volume":" ","pages":"733-743"},"PeriodicalIF":3.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0