Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.

IF 3.5 4区医学 Q3 CELL BIOLOGY

Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-05 DOI:10.1159/000533877

Takayuki Aiba, Naoki Hijiya, Tomonori Akagi, Yoshiyuki Tsukamoto, Yuka Hirashita, Keisuke Kinoshita, Tomohisa Uchida, Chisato Nakada, Shusaku Kurogi, Yoshitake Ueda, Hidefumi Shiroshita, Norio Shiraishi, Kazunari Murakami, Masafumi Inomata, Masatsugu Moriyama

{"title":"Overexpression of VSNL1 Enhances Cell Proliferation in Colorectal Carcinogenesis.","authors":"Takayuki Aiba, Naoki Hijiya, Tomonori Akagi, Yoshiyuki Tsukamoto, Yuka Hirashita, Keisuke Kinoshita, Tomohisa Uchida, Chisato Nakada, Shusaku Kurogi, Yoshitake Ueda, Hidefumi Shiroshita, Norio Shiraishi, Kazunari Murakami, Masafumi Inomata, Masatsugu Moriyama","doi":"10.1159/000533877","DOIUrl":null,"url":null,"abstract":"Introduction: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis.Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses.Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells.Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"121-131"},"PeriodicalIF":3.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pathobiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000533877","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/5 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: We have previously reported that overexpression of visinin-like protein 1 (VSNL1) is frequently observed in advanced colorectal adenocarcinomas and correlates with poorer prognosis. In this study, we determined the levels of VSNL1 expression in the earlier stages of colorectal tumors including adenomas and adenocarcinomas, and attempted to clarify the functional significance of VSNL1 overexpression in colorectal carcinogenesis.

Methods: Levels of VSNL expression in colorectal tumor tissues were analyzed using immunohistochemistry. The effects of VSNL1 downregulation and overexpression on cell proliferation, resistance to apoptosis, and invasiveness were determined using two VSNL1-overexpressing colorectal cancer cell lines, CW-2 and HCT-116 and VSNL1 inducibly expressing SNU-C5, respectively. Gene expression signatures in VSNL1-downregulated CW-2 and HCT-116 were identified using transcriptome and gene set enrichment analyses.

Results: VSNL1 expression was restricted to only a few crypt cells in the non-tumorous epithelium, whereas it became enhanced in adenomas and adenocarcinomas with the progression of tumorigenesis. Downregulation of VSNL1 in CW-2 and HCT-116 cells suppressed their proliferation through induction of apoptosis. Conversely, overexpression of VSNL1 in SNU-C5 cells enhanced resistance to anoikis. Transcriptome and gene set enrichment analyses revealed that downregulation of VSNL1 altered the expression level of the apoptosis-related gene set in CW-2 and HCT-116 cells.

Conclusion: VSNL1 plays a role in both the development and progression of colorectal tumors by enhancing cell viability.

查看原文本刊更多论文

VSNL1的过表达增强了结直肠癌发生过程中的细胞增殖。

引言：我们以前报道过VSNL1（Visinin样蛋白1）的过表达在晚期结直肠癌中经常观察到，并与较差的预后相关。在本研究中，我们测定了VSNL1在结直肠肿瘤早期（包括腺瘤和腺癌）中的表达水平，并试图阐明VSNL1过表达在结直肠癌变中的功能意义。方法：应用免疫组织化学方法分析VSNL在结直肠肿瘤组织中的表达水平。使用两种VSNL1过表达结直肠癌癌症细胞系CW-2和HCT116以及VSNL1诱导表达SNU-C5，分别测定了VSNL1下调和过表达对细胞增殖、抗凋亡和侵袭性的影响。使用转录组和基因集富集分析鉴定了VSNL1下调的CW-2和HCT116中的基因表达特征。结果：VSNL1在非肿瘤上皮中的表达仅限于少数隐窝细胞，而在腺瘤和腺癌中随着肿瘤发生的进展而增强。VSNL1在CW-2和HCT116细胞中的下调通过诱导细胞凋亡来抑制其增殖。相反，SNU-C5细胞中VSNL1的过表达增强了对失巢细胞的抗性。转录组和基因集富集分析显示，VSNL1的下调改变了CW-2和HCT116细胞中凋亡相关基因集的表达水平。结论：VSNL1通过提高细胞活力在结直肠癌的发生和发展中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Pathobiology 医学-病理学

CiteScore

8.50

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.