The lncRNA MALAT1 contributes to non‐small cell lung cancer development via modulating miR‐124/STAT3 axis

Abstract

lncRNAs can exert many biological effects in several cancer types. MALAT1 is a kind of lncRNA which is greatly overexpressed in several tumors including non-small cell lung cancer (NSCLC). However, the mechanism of MALAT1 in NSCLC still remains unclear. In our current study, we concentrated on the biological mechanism of MALAT1 in NSCLC. It was observed that MALAT1 was significantly upregulated in five human NSCLC cells including A549, H23, H522, H1299, and H460 cells compared to normal bronchial epithelial cell line 16HBE cells. On the contrary, miR-124 was remarkably downregulated, which indicated a potential negative correlation between miR-124 and MALAT1. MALAT1 inhibition can increase miR-124 expression in A549 and H460 cells. In addition, miR-124 mimics were able to repress MALAT1 expression and miR124 inhibitors can promote MALAT1 levels. Then it was found that shMALAT1 can inhibit NSCLC cell proliferation, colony formation and apoptosis, which can be reversed by miR-124 inhibitors. Bioinformatic analysis predicted the correlation between miR-124 and MALAT1. In addition, STAT3 was found to be a novel mRNA target of miR-124. Downregulation of MALAT1 can inhibit NSCLC development by enhancing miR-124 and decreasing STAT3 expression. We speculated that MALAT1can act as a competing endogenous lncRNA (ceRNA) to modulate miR-124/STAT3 in NSCLC. Taken these together, we revealed that MALAT1/miR-124/STAT3 was involved in NSCLC development.

Gastric Adenocarcinoma Predictive Long Intergenic Non-Coding RNA Promotes Tumor Occurrence and Progression in Non-Small Cell Lung Cancer via Regulation of the miR-661/eEF2K Signaling Pathway

“…For example, lncRNA MALAT1 is significantly up-regulated in 5 kinds of human NSCLC cells. Bioinformatic analysis has predicted a correlation between miR-124 and MALAT1 and indicated that STAT3 is the new mRNA target of miR-124 [24]. In this study, the results of bioinformatic tools on line and luciferase experiments showed that miR-661 targeted the 3'-UTR of lncRNA GAPLINC, and GAPLINC served as a molecular sponge for miR-661.…”

Knockdown of UCA1 inhibits viability and glycolysis by suppressing PKM2 expression through the mTOR pathway in non-small cell lung cancer cells

“…7,8 Convincing evidence has demonstrated that a large amount of lncRNAs are frequently dysregulated in human cancers and contribute to tumor development and progression. 9 Currently, multiple lncRNAs, such as lncRNA HNF1A-AS1, 10 MIAT, 11 and MALAT1, 12 have been identied to be involved in NSCLC progression. Human urothelial carcinoma associated 1 (UCA1), located at chromosome 19p13.12 with 1.4 kb in length, is a wellcharacterized lncRNA that was initially identied in human bladder carcinoma.…”

Lnc-DC regulates cellular turnover and the HBV-induced immune response by TLR9/STAT3 signaling in dendritic cells

“…The correlation between Lnc-RNAs and STAT3 signaling has been described in multiple tumor cells [18–20]. In this study, we elucidated the role of Lnc-DC in dendritic cells mediated by TLR9/STAT3 signaling.…”