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 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.

• Authors: 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
• Journal: BMC cancer (BMC Cancer) Vol. 21 Issue 1 Pg. 1218 (Nov 13 2021) ISSN: 1471-2407 [Electronic] England
• PMID: 34774019 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• DNA-Binding Proteins
• Histone Chaperones
• KLF4 protein, human
• Kruppel-Like Factor 4
• MIRN1915 microRNA, human
• MicroRNAs
• Neoplasm Proteins
• RNA-Binding Proteins
• SET protein, human
• YTHDF2 protein, human
• Methyltransferases
• METTL3 protein, human

Topics

• A549 Cells
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, mortality, pathology)
• Cell Movement (genetics)
• DNA-Binding Proteins (antagonists & inhibitors, genetics, metabolism)
• Down-Regulation
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression
• Genes, Reporter
• Genes, Tumor Suppressor (physiology)
• Histone Chaperones (antagonists & inhibitors, genetics, metabolism)
• Humans
• Kruppel-Like Factor 4 (genetics, metabolism)
• Lung Neoplasms (genetics, metabolism, mortality, pathology)
• Male
• Methyltransferases (genetics, metabolism)
• MicroRNAs (genetics, physiology)
• Middle Aged
• Neoplasm Invasiveness (genetics)
• Neoplasm Proteins (genetics, metabolism)
• RNA-Binding Proteins (genetics, metabolism)