MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway.

Zengliang Li,Hao Fan,Zekuan Xu,Wangwang Chen,Li Yang,Xiang Ma,Peidong Ni,Jian Xiao

doi:10.3389/fmolb.2021.655580

Abstract

MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.

Highlights

Gastric cancer (GC) is one of the most prevalent and deadly cancer types worldwide, in East Asia (Sung et al, 2021)
Our study showed that miR-653-5p-mediated GC progression and metastasis through modulation of the Suppressor of cytokine signaling 6 (SOCS6)-STAT3 signaling pathway, highlighting potential novel diagnostic and therapeutic targets for GC
Based on the significantly increased expression, and a strong association with poor prognosis, of miR-653-5p in GC as determined via analysis of the The Cancer Genome Atlas Program (TCGA) database (Figures 1C– E and Supplementary Figure 1C), we further evaluated the expression level of miR-653-5p in 80 paired GC tissues and adjacent normal tissues using reverse transcription and qRTPCR

Summary

Introduction

Gastric cancer (GC) is one of the most prevalent and deadly cancer types worldwide, in East Asia (Sung et al, 2021). MiRNAs bind complementary mRNA sequences to repress expression via degradation of posttranscriptional mRNA or inhibition of translation (Ha and Kim, 2014). Dysregulated expression of miRNAs has been linked to various diseases, including onset and progression of different types of cancer (Lee and Dutta, 2009). The recent advent of genomics and novel sequencing approaches has resulted in the identification of key miRNAs involved in proliferation, metastasis, and drug resistance of GC cells through actions as oncogenes or tumor suppressors (Wu et al, 2010; Liu et al, 2020). A study showed that loss of miR-29c expression, which acts as a tumor suppressor via direct targeting ITGB1, was an early event in the initiation of gastric carcinogenesis (Han et al, 2015)

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