MiR-21 Overexpression Promotes Esophageal Squamous Cell Carcinoma Invasion and Migration by Repressing Tropomyosin 1

Zhuojian Shen,Liangzhan Lv,Ju Chen,Honglue Dai,Baishen Chen,Xia Xu,Eiji Sakai

doi:10.1155/2020/6478653

Zhuojian Shen, Liangzhan Lv + Show 5 more

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https://doi.org/10.1155/2020/6478653

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Abstract

The migration and invasion of esophageal squamous cell carcinoma are associated with clinical outcomes, however, the mechanisms remain poorly understood. Here, we found that miR-21 is significantly overexpressed in ESCC, lung cancer, and bladder cancer compared with the adjacent normal tissue. MiR-21 and TPM1 expressions were analyzed by RT-qPCR and WB in 30 ESCC, 10 lung cancer, and 10 bladder cancer clinical specimens, each with matched adjacent normal tissue. Knockdown and overexpression of miR-21 as well as knockdown of TPM1 in ESCC cell lines were performed using synthetic oligonucleotides. TPM1 3′UTR luciferase reporter constructs were used to investigate targeting of TPM1 by miR-21. ESCC migration and invasion were assessed using transwell migration and invasion assays. Inhibition of miR-21 reduced migration and invasion in two ESCC cell lines, and overexpression of miR-21 promoted migration and invasion in vitro. Interestingly, TPM1 exhibited inverse patterns of expression compared with miR-21 in tissues and cell lines. Luciferase reporter assays demonstrated that TPM1 was directly regulated by miR-21. Moreover, the forced overexpression of miR-21 repressed the TPM1 expression, while silencing of miR-21 restored the TPM1 expression in ESCC cell lines. What is more, simultaneous silencing of miR-21 and TPM1 expressions did not alter the migratory and invasive characteristics demonstrating that the effects of miR-21 were mediated through TPM1. In conclusion, the aberrant overexpression of miR-21 is common in cancer and promotes the migration and invasion of ESCC through inhibiting the TPM1 expression. These results suggest that miR-21 may be a novel predictive marker and therapeutic target for treatment of ESCC.

Highlights

MicroRNAs are naturally occurring short, noncoding RNA molecules, 21-23 nucleotides long, that regulate the gene expression by binding to mRNAs either to suppress translation or to initiate degradation of target transcripts [1]
The miR-21 expression was significantly higher in all 30 Esophageal squamous cell carcinoma (ESCC) samples and in all 10 lung cancer samples compared to paired adjacent normal tissue samples (Figures 1(a) and 1(b))
These results demonstrate that the aberrant overexpression of miR-21 may be a common phenomenon in cancer, especially in ESCC, and suggest that miR-21 may play an essential role in various malignant processes in ESCC

Summary

Introduction

MicroRNAs (miRNAs) are naturally occurring short, noncoding RNA molecules, 21-23 nucleotides long, that regulate the gene expression by binding to mRNAs either to suppress translation or to initiate degradation of target transcripts [1]. Since their initial identification, thousands of miRNAs have been identified in human genome. MiR-21 has been identified as a central onco-miRNA in tumor formation and is overexpressed in many solid tumors, including esophageal cancer [3,4,5]. Several biomarkers have been reported to be associated with the development of ESCC, including p53, cyclin D1, and miR-21 [5, 7, 8]

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