抑制 m6A 阅读器 IGF2BP3 可通过调节 PLAGL2 mRNA 稳定性抑制卵巢癌细胞生长

IF 2.1 Q3 ONCOLOGY World Journal of Oncology Pub Date : 2024-02-01 Epub Date: 2024-01-10 DOI:10.14740/wjon1747

Tian Tian Dai, Yi Ze Li, Hui Ting Hu, Yong Mei Zhao, Hong Yan Peng, Wen Dong Bai, Jing Wen Wang

{"title":"抑制 m6A 阅读器 IGF2BP3 可通过调节 PLAGL2 mRNA 稳定性抑制卵巢癌细胞生长","authors":"Tian Tian Dai, Yi Ze Li, Hui Ting Hu, Yong Mei Zhao, Hong Yan Peng, Wen Dong Bai, Jing Wen Wang","doi":"10.14740/wjon1747","DOIUrl":null,"url":null,"abstract":"Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.","PeriodicalId":46797,"journal":{"name":"World Journal of Oncology","volume":"15 1","pages":"100-113"},"PeriodicalIF":2.1000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807918/pdf/","citationCount":"0","resultStr":"{\"title\":\"Inhibiting the m6A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.\",\"authors\":\"Tian Tian Dai, Yi Ze Li, Hui Ting Hu, Yong Mei Zhao, Hong Yan Peng, Wen Dong Bai, Jing Wen Wang\",\"doi\":\"10.14740/wjon1747\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m6A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.\",\"PeriodicalId\":46797,\"journal\":{\"name\":\"World Journal of Oncology\",\"volume\":\"15 1\",\"pages\":\"100-113\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807918/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Oncology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.14740/wjon1747\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14740/wjon1747","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/10 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：肿瘤基因IGF2 mRNA结合蛋白3（IGF2BP3）可作为m6A阅读器稳定许多肿瘤相关基因的mRNA。然而，IGF2BP3促进卵巢癌生长的相关致癌机制尚不清楚：方法：通过检索癌症基因组图谱（The Cancer Genome Atlas，TCGA）中的数据集，确定卵巢癌中 IGF2BP3 的表达。GEO 数据集评估了卵巢癌细胞中 IGF2BP3 基因敲除的相关信号通路。计算了 TCGA 中的 IGF2BP3 正相关基因。MTS增殖试验发现，在ES-2和SKOV3细胞中，IGF2BP3敲除后，PLAG1 like zinc finger 2（PLAGL2）过表达可挽救细胞增殖。生物信息分析和 RIP-qPCR 预测并确定了 IGF2BP3 结合位点和 PLAGL2 mRNA 的稳定性。动物实验确定了 IGF2BP3 的增殖抑制作用：结果：IGF2BP3在卵巢癌组织和细胞中上调。结果：IGF2BP3 在卵巢癌组织和细胞中上调，消耗卵巢癌细胞中的 IGF2BP3 会导致细胞增殖和 mRNA 稳定的途径增强。IGF2BP3 正相关抑制促增殖基因 PLAGL2。IGF2BP3 基因敲除抑制了卵巢癌细胞的增殖，而 PLAGL2 基因过表达则可挽救这种抑制。荧光素酶报告实验证实，IGF2BP3能与PLAGL2的3'-UTR结合，维持mRNA的稳定性。此外，在体内实验中，敲除 IGF2BP3 可通过抑制 PLAGL2 的表达来抑制卵巢癌细胞的增殖：结论：所有这些都表明，PLAGL2 通过调节 mRNA 的稳定性介导了 IGF2BP3 敲除对卵巢癌增殖抑制的主要功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Inhibiting the m⁶A Reader IGF2BP3 Suppresses Ovarian Cancer Cell Growth via Regulating PLAGL2 mRNA Stabilization.

Background: The oncogene IGF2 mRNA binding protein 3 (IGF2BP3) could function as an m⁶A reader in stabilizing many tumor-associated genes' mRNAs. However, the relevant oncogenic mechanism by which IGF2BP3 promotes ovarian cancer growth is largely unknown.

Methods: The IGF2BP3 expression in ovarian cancer was identified by retrieving the datasets from The Cancer Genome Atlas (TCGA). GEO datasets evaluated the relevant signaling pathways in IGF2BP3 knockdown in ovarian cancer cells. IGF2BP3 positive correlation gene in TCGA was calculated. MTS proliferation assay was identified in IGF2BP3 knockdown and rescued by PLAG1 like zinc finger 2 (PLAGL2) overexpression in ES-2 and SKOV3 cells. Bioinformatic analysis and RIP-qPCR were predicted and identified the IGF2BP3 binding site and PLAGL2 mRNA stability. The animal experiment identified IGF2BP3 proliferation inhibition.

Results: IGF2BP3 was upregulated in ovarian cancer tissue and cells. The depletion of IGF2BP3 in ovarian cancer cells leads to an enhancement of the pathway involved in cellular proliferation and mRNA stability. IGF2BP3 positive correlation suppressed pro-proliferation gene PLAGL2. IGF2BP3 knockdown suppressed ovarian cancer cell proliferation and was rescued by PLAGL2 overexpression. Luciferase reporter assay confirmed that IGF2BP3 could bind to 3'-UTR of PLAGL2 to maintain the mRNA stability. Further, in in vivo experiments, IGF2BP3 knockdown suppressed ovarian cancer cell proliferation via inhibiting PLAGL2 expression.

Conclusion: All of these indicate that PLAGL2 mediates the main function of IGF2BP3 knockdown on ovarian cancer proliferation inhibition through mRNA stability regulation.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

World Journal of Oncology ONCOLOGY-

CiteScore

6.10

自引率

15.40%

发文量

期刊介绍： World Journal of Oncology, bimonthly, publishes original contributions describing basic research and clinical investigation of cancer, on the cellular, molecular, prevention, diagnosis, therapy and prognosis aspects. The submissions can be basic research or clinical investigation oriented. This journal welcomes those submissions focused on the clinical trials of new treatment modalities for cancer, and those submissions focused on molecular or cellular research of the oncology pathogenesis. Case reports submitted for consideration of publication should explore either a novel genomic event/description or a new safety signal from an oncolytic agent. The areas of interested manuscripts are these disciplines: tumor immunology and immunotherapy; cancer molecular pharmacology and chemotherapy; drug sensitivity and resistance; cancer epidemiology; clinical trials; cancer pathology; radiobiology and radiation oncology; solid tumor oncology; hematological malignancies; surgical oncology; pediatric oncology; molecular oncology and cancer genes; gene therapy; cancer endocrinology; cancer metastasis; prevention and diagnosis of cancer; other cancer related subjects. The types of manuscripts accepted are original article, review, editorial, short communication, case report, letter to the editor, book review.