LncRNA MALAT1 Regulating Lung Carcinoma Progression via the miR-491-5p/UBE2C Axis.

Juanjuan Dai,Rui Wu,Kaikai Gong,Lijuan Yang,Shuang Miao,Weiwei Chen,Xuelin Li,Chen Li,Yan Wu,Jing Du,Ning Zhou

doi:10.3389/pore.2021.610159

Juanjuan Dai, Rui Wu + Show 9 more

Open Access

https://doi.org/10.3389/pore.2021.610159

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Abstract

Long noncoding RNAs (lncRNAs) play a critical role in the development of lung carcinoma. The mechanism of MALAT1 in lung carcinoma development is not understood very well. This study aimed to investigate the role of MALAT1 in lung carcinoma progression and the mechanism underlying the role of miR-491-5p in the MALAT1 mediated regulation of UBE2C expression. The results indicated that the expression of MALAT1 was often augmented in lung carcinoma cells. Suppression of MALAT1 blocked the proliferation, invasion and migration ability of cancer cells and inhibited the expression of UBE2C. UBE2C restoration attenuated the MALAT1 knockdown-induced anti-cancer effects. Moreover, UBE2C and MALAT1 were indicated as targets of miR-491-5p and inhibition of miR-491-5p restored the MALAT1 knockdown-induced inhibition of the progression of lung carcinoma. Furthermore, MALAT1 sponged miR-491-5p to upregulate UBE2C expression, causing it to act as a competing endogenous RNA. Collectively, MALAT1 downregulation suppressed lung carcinoma progression by regulating the miR-491-5p/UBE2C axis. These results indicate that MALAT1 could be a molecular target for lung carcinoma treatment and prognosis.

Highlights

Lung carcinoma is among the leading causes of cancer-related deaths in China and worldwide [1, 2]
The long noncoding RNA MALAT1 is overexpressed in numerous cancers and plays a key role in cell proliferation and metastasis via the modulation of the PI3K/AKT [22], NFkB [23], WNT/β-catenin [24], MAKP/ERK [25] and other molecular signaling pathways
We showed that MALAT1 knockdown blocked the proliferation, colony formation, FIGURE 5 | Knockdown of MALAT1 inhibited the progression of lung cancer, which was induced by the miR-491-5p inhibitor. (A) CCK-8 assay was performed to evaluate cell proliferation. (B) Colony formation assay demonstrating that the miR-491-5p inhibitor markedly increased the MALAT1 knockdown-induced suppression of colony formation ability in H1299 and H520 cells. (C,D) Transwell assay performed with (C) or without matrigel (D) indicated that the miR-491-5p inhibitor promotes the invasion and migration abilities of H1299 and H520 cells via the regulation of MALAT1. *p < 0.05, **p < 0.01, ***p < 0.001

Summary

Introduction

Lung carcinoma is among the leading causes of cancer-related deaths in China and worldwide [1, 2]. Long non-coding RNAs (lncRNAs) have little or no protein-coding capacity and their length is >200 nucleotides [5]. Recent studies have indicated that lncRNAs may affect many cellular physiological processes, including the cell cycle, apoptosis, migration, senescence and chemoresistance [6,7,8,9]. With a length of >8,000 nucleotides, MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), known as NEAT2 (nuclear enriched abundant transcript 2), is one of the first tumor metastasis-associated and highly conserved lncRNAs to be discovered. A large amount of evidence has shown that MALAT1 plays an important role in the tumorigenesis of many types of tumors, including lung carcinoma, breast cancer and pancreatic cancer [10,11,12]. Abundant research has indicated that MALAT1 acts as a “sponge,”

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