ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells

被引：6

作者：

Yang, Jiong ^{[1
]}

Liu, Xinli ^{[2
]}

Sun, Yang ^{[2
]}

Zhang, Xutao ^{[3
]}

Zhao, Yong ^{[4
]}

Zhang, Haihua ^{[5
]}

Mei, Qibing ^{[2
]}

Meng, Jin ^{[1
]}

Zhang, Feng ^{[2
]}

Zhang, Tao ^{[5
]}

机构：

[1] Peoples Liberat Army Gen Hosp, Med Supplies Ctr, Beijing 100853, Peoples R China

[2] Air Force Med Univ, Sch Pharm, State Adm Tradit Chinese Med, Dept Pharmacol,Key Lab Gastrointestinal Pharmacol, Xian 710032, Peoples R China

[3] Air Force Med Univ, Dept Clin Aerosp Med, Xian 710032, Peoples R China

[4] Air Force Med Univ, Lab Anim Ctr, Xian 710032, Peoples R China

[5] Air Force Med Univ, Tangdu Hosp, Dept Thorac Surg, Xian 710038, Peoples R China

来源：

ACTA BIOCHIMICA ET BIOPHYSICA SINICA | 2023年 / 55卷 / 05期

基金：

中国国家自然科学基金;

关键词：

inhibitor of growth protein 5 (ING5); miR-34c-5p; non-small cell lung cancer (NSCLC); invasion and metastasis; diagnostic and prognostic biomarkers; EPITHELIAL-MESENCHYMAL TRANSITION; FAMILY;

D O I：

10.3724/abbs.2023074

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

ING5 belongs to the inhibitor of growth (ING) candidate tumor suppressor family, which is involved in multiple cellular functions, such as cell cycle regulation, apoptosis, and chromatin remodelling. Previously, we reported that ING5 overexpression inhibits EMT by regulating EMT-related molecules, including Snail1, at the mRNA and protein levels. However, the mechanisms remain unclear. In the current study, we identify that ING5 overexpression induces the upregulation of miR-34c-5p. The expression levels of both ING5 and miR-34c-5p in NSCLC tissues from the TCGA database are decreased compared with that in adjacent tissues. Higher expression levels of both ING5 and miR-34c-5p predict longer overall survival (OS). Snail1 is the target gene of miR-34c-5p, as predicted by an online database, which is further verified by a dual-luciferase reporter assay. The expression level of Snail1 in NSCLC cells is markedly reduced following miR-34c-5p overexpression, leading to the inactivation of the Snail1 downstream TGF-beta/Smad3 signaling pathway. The TGF-beta signaling-specific inhibitor LY2157299 reverses the enhanced EMT, proliferation, migration, and invasion abilities induced by the miR-34c-5p inhibitor. Furthermore, tail vein injection of miR-34c-5p agomir inhibits xenografted tumor metastasis. Overall, this study concludes that miR-34c-5p, induced by ING5 overexpression, is a tumor suppressor that targets Snail1 and mediates the inhibitory effects of ING5 on the EMT and invasion of NSCLC cells. These results provide a novel mechanism mediating the antitumor effects of ING5.

引用

页码：809 / 817

页数：9