IGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell Pub Date : 2024-12-31 DOI:10.1016/j.tice.2024.102716

Fang Li, Yadong Zhou, Zhiming Liao, Da Huang, Ziqing Zhang, Guoqun Chen

{"title":"IGF2BPs-regulated TIN2 confers the malignant biological behaviors of gastric cancer cells","authors":"Fang Li, Yadong Zhou, Zhiming Liao, Da Huang, Ziqing Zhang, Guoqun Chen","doi":"10.1016/j.tice.2024.102716","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Telomere maintenance is an important feature of tumor cells. Telomeric-repeat binding factor 1 interaction nuclear protein 2 (TIN2), a key member of the shelterin proteins, functions in regulating telomere structure, length and function. Our work sought to investigate the role of TIN2 in controlling gastric cancer (GC) malignant biological behaviors.</div></div><div><h3>Methods</h3><div>The mRNA and protein expressions were examined by qRT-PCR, western blot and immunofluorescence assays. The relative telomerase activity and telomere length were detected using the corresponding kit and qRT-PCR, respectively. The proliferation, migration and invasion abilities were detected by CCK8 and transwell assays, respectively. Cellular oxidative stress level and Fe<sup>2 +</sup> content were assessed by DCFH-DA staining and ELISA assays, respectively. The interaction between IGF2BP1/2/3 and TIN2 was analyzed by RIP and RNA pull down assays.</div></div><div><h3>Results</h3><div>TIN2 expression was significantly increased in GC cells compared with it in gastric mucosal epithelial cells. TIN2 knockdown could impair telomerase function and induce DNA injury in GC cells. Moreover, silencing of TIN2 greatly repressed cell proliferation, metastasis, and autophagy in GC cells. Likewise, the antioxidant capacity and Fe<sup>2+</sup> content were enhanced after TIN2 depletion, leading to the activation of cellular ferroptosis. In terms of mechanism, TIN2 mRNA could be recognized by IGF2BP1/2/3, and its mRNA expression and stability were decreased upon IGF2BP1/2/3 was knocked down.</div></div><div><h3>Conclusion</h3><div>Knockdown of TIN2 could restrained telomerase function and the malignant abilities of proliferation, metastasis and autophagy but induced ferroptosis of GC cells, which suggested that targeting TIN2 might be a therapeutic strategy for GC</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"93 ","pages":"Article 102716"},"PeriodicalIF":2.7000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tissue & cell","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040816624004178","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ANATOMY & MORPHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Telomere maintenance is an important feature of tumor cells. Telomeric-repeat binding factor 1 interaction nuclear protein 2 (TIN2), a key member of the shelterin proteins, functions in regulating telomere structure, length and function. Our work sought to investigate the role of TIN2 in controlling gastric cancer (GC) malignant biological behaviors.

Methods

The mRNA and protein expressions were examined by qRT-PCR, western blot and immunofluorescence assays. The relative telomerase activity and telomere length were detected using the corresponding kit and qRT-PCR, respectively. The proliferation, migration and invasion abilities were detected by CCK8 and transwell assays, respectively. Cellular oxidative stress level and Fe^2 + content were assessed by DCFH-DA staining and ELISA assays, respectively. The interaction between IGF2BP1/2/3 and TIN2 was analyzed by RIP and RNA pull down assays.

Results

TIN2 expression was significantly increased in GC cells compared with it in gastric mucosal epithelial cells. TIN2 knockdown could impair telomerase function and induce DNA injury in GC cells. Moreover, silencing of TIN2 greatly repressed cell proliferation, metastasis, and autophagy in GC cells. Likewise, the antioxidant capacity and Fe²⁺ content were enhanced after TIN2 depletion, leading to the activation of cellular ferroptosis. In terms of mechanism, TIN2 mRNA could be recognized by IGF2BP1/2/3, and its mRNA expression and stability were decreased upon IGF2BP1/2/3 was knocked down.

Conclusion

Knockdown of TIN2 could restrained telomerase function and the malignant abilities of proliferation, metastasis and autophagy but induced ferroptosis of GC cells, which suggested that targeting TIN2 might be a therapeutic strategy for GC

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Tissue & cell 医学-解剖学与形态学

CiteScore

3.90

自引率

0.00%

发文量

234

期刊介绍： Tissue and Cell is devoted to original research on the organization of cells, subcellular and extracellular components at all levels, including the grouping and interrelations of cells in tissues and organs. The journal encourages submission of ultrastructural studies that provide novel insights into structure, function and physiology of cells and tissues, in health and disease. Bioengineering and stem cells studies focused on the description of morphological and/or histological data are also welcomed. Studies investigating the effect of compounds and/or substances on structure of cells and tissues are generally outside the scope of this journal. For consideration, studies should contain a clear rationale on the use of (a) given substance(s), have a compelling morphological and structural focus and present novel incremental findings from previous literature.