MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer

Abstract Background MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. Methods The expression...

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Autores principales: Hongli Pan, Zhenhua Pan, Fengjie Guo, Fanrong Meng, Lingling Zu, Yaguang Fan, Yang Li, Mengjie Li, Xinxin Du, Xiuwen Zhang, Yi Shao, Mingming Wei, Xuebing Li, Qinghua Zhou
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Publicado: BMC 2021
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spelling oai:doaj.org-article:c7ef73183b9c4453afa82643468b845d2021-11-14T12:29:58ZMicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer10.1186/s12885-021-08961-81471-2407https://doaj.org/article/c7ef73183b9c4453afa82643468b845d2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12885-021-08961-8https://doaj.org/toc/1471-2407Abstract Background MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. Methods The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). Results miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3′untranslated region (3′UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What’s more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. Conclusions These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.Hongli PanZhenhua PanFengjie GuoFanrong MengLingling ZuYaguang FanYang LiMengjie LiXinxin DuXiuwen ZhangYi ShaoMingming WeiXuebing LiQinghua ZhouBMCarticleNSCLCmiR-1915-3pInvasionMigrationSETNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBMC Cancer, Vol 21, Iss 1, Pp 1-16 (2021)
institution DOAJ
collection DOAJ
language EN
topic NSCLC
miR-1915-3p
Invasion
Migration
SET
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle NSCLC
miR-1915-3p
Invasion
Migration
SET
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Hongli Pan
Zhenhua Pan
Fengjie Guo
Fanrong Meng
Lingling Zu
Yaguang Fan
Yang Li
Mengjie Li
Xinxin Du
Xiuwen Zhang
Yi Shao
Mingming Wei
Xuebing Li
Qinghua Zhou
MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
description Abstract Background MicroRNAs (miRNAs) have been reported to play significant roles in non-small-cell lung cancer (NSCLC). However, the roles of microRNA (miR)-1915-3p in NSCLC remain unclear. In this study, we aimed to explore the biological functions of miR-1915-3p in NSCLC. Methods The expression of miR-1915-3p and SET nuclear proto-oncogene (SET) in NSCLC tissues were examined by quantitative real-time PCR (qRT-PCR). Migratory and invasive abilities of lung cancer were tested by wound healing and transwell invasion assay. The direct target genes of miR-1915-3p were measured by dual-luciferase reporter assay and western blot. Finally, the regulation between METTL3/YTHDF2/KLF4 axis and miR-1915-3p were evaluated by qRT-PCR, promoter reporter assay and chromatin immunoprecipitation (CHIP). Results miR-1915-3p was downregulated in NSCLC tissues and cell lines, and inversely associated with clinical TNM stage and overall survival. Functional assays showed that miR-1915-3p significantly suppressed migration, invasion and epithelial-mesenchymal transition (EMT) in NSCLC cells. Furthermore, miR-1915-3p directly bound to the 3′untranslated region (3′UTR) of SET and modulated the expression of SET. SET inhibition could recapitulate the inhibitory effects on cell migration, invasion and EMT of miR-1915-3p, and restoration of SET expression could abrogate these effects induced by miR-1915-3p through JNK/Jun and NF-κB signaling pathways. What’s more, miR-1915-3p expression was regulated by METTL3/YTHDF2 m6A axis through transcription factor KLF4. Conclusions These findings demonstrate that miR-1915-3p function as a tumor suppressor by targeting SET and may have an anti-metastatic therapeutic potential for lung cancer treatment.
format article
author Hongli Pan
Zhenhua Pan
Fengjie Guo
Fanrong Meng
Lingling Zu
Yaguang Fan
Yang Li
Mengjie Li
Xinxin Du
Xiuwen Zhang
Yi Shao
Mingming Wei
Xuebing Li
Qinghua Zhou
author_facet Hongli Pan
Zhenhua Pan
Fengjie Guo
Fanrong Meng
Lingling Zu
Yaguang Fan
Yang Li
Mengjie Li
Xinxin Du
Xiuwen Zhang
Yi Shao
Mingming Wei
Xuebing Li
Qinghua Zhou
author_sort Hongli Pan
title MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
title_short MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
title_full MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
title_fullStr MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
title_full_unstemmed MicroRNA-1915-3p inhibits cell migration and invasion by targeting SET in non-small-cell lung cancer
title_sort microrna-1915-3p inhibits cell migration and invasion by targeting set in non-small-cell lung cancer
publisher BMC
publishDate 2021
url https://doaj.org/article/c7ef73183b9c4453afa82643468b845d
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