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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2021
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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) |
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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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