Zhuxin Gu, Yanjun Sun, Fajing Chen, Weiwei Gu, Xiaohua Lu, Suming Zhao, Qinan Geng, Yang Yang
{"title":"LINC00519/hsa-miR-22-3p/MECOM轴通过PI3K/AKT信号通路加速肝内胆管癌进展","authors":"Zhuxin Gu, Yanjun Sun, Fajing Chen, Weiwei Gu, Xiaohua Lu, Suming Zhao, Qinan Geng, Yang Yang","doi":"10.1158/1541-7786.MCR-25-0207","DOIUrl":null,"url":null,"abstract":"<p><p>Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays prominent roles in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, LINC00519, hsa-miR-22-3p, and MECOM expressions in ICC were assessed with ENCORI database and quantitative real-time PCR. Biological functions of LINC00519 in ICC were examined using clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the LINC00519 mechanism in ICC was determined by dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, but hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation, migration and induced cell apoptosis. Also, LINC00519 knockdown repressed PI3K/AKT pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration, and accelerated apoptosis through PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. Implications: This study deepens the understanding of the non-coding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.</p>","PeriodicalId":19095,"journal":{"name":"Molecular Cancer Research","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The LINC00519/hsa-miR-22-3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression Through PI3K/AKT Signaling.\",\"authors\":\"Zhuxin Gu, Yanjun Sun, Fajing Chen, Weiwei Gu, Xiaohua Lu, Suming Zhao, Qinan Geng, Yang Yang\",\"doi\":\"10.1158/1541-7786.MCR-25-0207\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays prominent roles in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, LINC00519, hsa-miR-22-3p, and MECOM expressions in ICC were assessed with ENCORI database and quantitative real-time PCR. Biological functions of LINC00519 in ICC were examined using clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the LINC00519 mechanism in ICC was determined by dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, but hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation, migration and induced cell apoptosis. Also, LINC00519 knockdown repressed PI3K/AKT pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration, and accelerated apoptosis through PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. Implications: This study deepens the understanding of the non-coding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.</p>\",\"PeriodicalId\":19095,\"journal\":{\"name\":\"Molecular Cancer Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Cancer Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1541-7786.MCR-25-0207\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Cancer Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1541-7786.MCR-25-0207","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
The LINC00519/hsa-miR-22-3p/MECOM Axis Accelerates Intrahepatic Cholangiocarcinoma Progression Through PI3K/AKT Signaling.
Intrahepatic cholangiocarcinoma (ICC) is the second most common liver cancer. LINC00519 plays prominent roles in the progression of numerous cancers. To explore the molecular mechanism of LINC00519 in ICC, LINC00519, hsa-miR-22-3p, and MECOM expressions in ICC were assessed with ENCORI database and quantitative real-time PCR. Biological functions of LINC00519 in ICC were examined using clone formation experiment, Transwell analysis, flow cytometry, and Western blot. Meanwhile, the LINC00519 mechanism in ICC was determined by dual-luciferase reporter assay. Results showed that LINC00519 and MECOM were highly expressed in ICC, but hsa-miR-22-3p was decreased. Functionally, silencing LINC00519 weakened ICC cell proliferation, migration and induced cell apoptosis. Also, LINC00519 knockdown repressed PI3K/AKT pathway. Mechanistically, LINC00519 acted as a competitive endogenous RNA to target MECOM by sponging hsa-miR-22-3p. Meanwhile, rescue assays further proved that low LINC00519 expression restrained ICC cell proliferation and migration, and accelerated apoptosis through PI3K/AKT pathway by miR-22-3p/MECOM. In conclusion, this research revealed a novel LINC00519/hsa-miR-22-3p/MECOM regulatory axis and PI3K/AKT pathway that modulated ICC progression. Implications: This study deepens the understanding of the non-coding RNA regulatory network in ICC and provides potential targets for the diagnosis and targeted therapy of ICC.
期刊介绍:
Molecular Cancer Research publishes articles describing novel basic cancer research discoveries of broad interest to the field. Studies must be of demonstrated significance, and the journal prioritizes analyses performed at the molecular and cellular level that reveal novel mechanistic insight into pathways and processes linked to cancer risk, development, and/or progression. Areas of emphasis include all cancer-associated pathways (including cell-cycle regulation; cell death; chromatin regulation; DNA damage and repair; gene and RNA regulation; genomics; oncogenes and tumor suppressors; signal transduction; and tumor microenvironment), in addition to studies describing new molecular mechanisms and interactions that support cancer phenotypes. For full consideration, primary research submissions must provide significant novel insight into existing pathway functions or address new hypotheses associated with cancer-relevant biologic questions.