Abstract
Background: The abnormal expression of miRNAs facilitates tumorigenesis and development. miR-181a-2-3p is up-regulated in various cancers, yet its mechanism in gastric cancer (GC) remains elusive. Objective: To understand mechanism of miR-181a-2-3p stimulating GC cell progression via targeting Myosin Light Chain Kinase (MYLK) expression. Methods: Downstream genes of miRNA of interest were predicted in TargetScan and miRTarBase. qRT-PCR and western blot were applied to assess miR-181a-2-3p and MYLK expression in GC cells and normal cells. Dual-luciferase and RIP assays were completed to assess binding of miR-181a-2-3p and MYLK. Cell Counting Kit-8 (CCK-8) assay was conducted for detecting viability of AGS and SNU-1 cells, while Transwell tested migratory and invasive abilities of cells. Nude mouse transplantation tumor experiment was performed to assay tumor growth in vivo. Results: miR-181a-2-3p was notably increased in human GC cell lines, while MYLK was remarkably down-regulated. RIP and dual-luciferase assay disclosed that miR-181a-2-3p targeted MYLK and repressed MYLK. Forced miR-181a-2-3p expression fostered GC cell proliferation, invasion, migration, and fostered tumor growth in vivo. Promoting effect of miR-181a-2-3p on GC cells was reversed when miR-181a-2-3p and MYLK were simultaneously overexpressed. Conclusion: miR-181a-2-3p facilitated GC cell progression by targeting MYLK, and it may be a pivotal prognostic biomarker in investigating molecular mechanism of GC.
Highlights
Gastric cancer (GC) is a frequent malignancy with a low survival rate (Smyth et al, 2020)
We found that miR-181a-2-3p had a great potential to promote GC epithelial cell proliferation, invasion, and migration via modulating Myosin light chain kinase (MYLK) expression
MiR-181a-2-3p is Highly Expressed in GC Cells
Summary
Gastric cancer (GC) is a frequent malignancy with a low survival rate (Smyth et al, 2020). Research has evinced that miRNAs are associated with regulatory processes of promoting or inhibiting cancer cells by serving as biomarkers for management ofcancers (Lee and Dutta, 2009; Mishra et al, 2016; Liu et al, 2018). MiRNAs act as modulators in diverse biological processes like cell differentiation, proliferation, metabolism, and cancer development (Shin and Chu, 2014; Khan et al, 2019). The forced miR-18a-3p expression and miR-4286 can repress BZRAP1 to enhance proliferation and movement of GC cells, leading to tumor progression in vitro (Liu et al, 2019; Tsai et al, 2020), whereas miR-320a suppresses the progression of GC by targeting PBX3 (Li et al, 2019). The abnormal expression of miRNAs facilitates tumorigenesis and development. miR-181a-2-3p is up-regulated in various cancers, yet its mechanism in gastric cancer (GC) remains elusive
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