Assessing the Regulatory Functions of LncRNA SNHG11 in Gastric Cancer Cell Proliferation and Migration.

Danyi Zhao,Bing Wang,Huawei Chen

doi:10.3389/fcell.2021.620476

Abstract

The aim of this study was to assess the regulatory functions of SNHG11 in gastric cancer (GC) cell proliferation and migration. Dual-luciferase reporter assay and bioinformatics prediction [starBase (http://starbase.sysu.edu.cn/) and TargetScan (http://www.targetscan.org)] indicated that SNHG11 functions as a miR-184 sponge that can directly act on CDC25A. Compared with normal healthy gastric tissue and mucosal epithelial cell GES-1, SNHG11 and CDC25A expressions were dramatically increased in GC samples and cell lines, whereas microRNA-184 (miR-184) levels were reduced. SNHG11 silencing led to increased miR-184 and reduced CDC25A, whereas miR-184 downregulation recovered the expression of CDC25A. Additionally, miR-184 upregulation also played a role in regulating CDC25A ablation. Then, SNHG11 was silenced or miR-184 was upregulated in two GC cells (SGC-7901 and MKN-28). SNHG11 silencing and miR-184 upregulation caused a notable decrease in GC cell growth and proliferation and increased the apoptotic level of GC cells. Furthermore, SNHG11 silencing and miR-184 upregulation contributed to a decreased migration capacity of GC cells. Downregulated miR-184 expression in SNHG11 silenced GC cells showed that miR-184 inhibition reversed the effect of SNHG11 silencing on the growth, proliferation, apoptosis, and migration of GC cells. Moreover, in vivo xenograft experiments demonstrated that SNHG11 knockdown can inhibit tumor growth. These observations confirmed that SNHG11 acts as an oncogene, whereas miR-194 served as a tumor suppressor in GC development. SNHG11 may provide a new biomarker for GC diagnosis, treatment, and prognosis.

Highlights

Gastric cancer (GC) is the fourth most prevalent cancer and the second biggest trigger of cancerrelated mortality in the world (Ferlay et al, 2010)
Several studies have demonstrated that long non-coding RNAs (lncRNAs) SNHG11 serves as a miR-184 sponge in hepatocellular cancer cells (Huang et al, 2020), whereas the latter targeted 3 -UTR of CDC25A in nonsmall cell lung cancer (Lin et al, 2015)
We found that SNHG11 and CDC25A were increased in gastric cancer (GC) cell lines, whereas miR-184 expression was downregulated compared with GES-1 cells (Figures 2D–G), suggesting that SNHG11, miR-184, and CDC25A play a role in GC development

Summary

Introduction

Gastric cancer (GC) is the fourth most prevalent cancer and the second biggest trigger of cancerrelated mortality in the world (Ferlay et al, 2010). The occurrence of GC involves many steps and factors, and identifying GC subtypes will pave the way for patient stratification and targeted therapy development (Wadhwa et al, 2013; Cancer Genome Atlas Research Network, 2014). Many studies have demonstrated that the prognosis for GC molecule or protein expression profiles are probably distinct (Chen et al, 2015). Four GC molecule subtypes (Epstein–Barr virus, microsatellite instability, chromosomal instability, and genomically stable) are currently associated with different patterns of molecule changes, disease progression, and prognosis according to gene expressions (Wadhwa et al, 2013; Cancer Genome Atlas Research Network, 2014). The molecular mechanisms underlying gastric occurrence are still unknown, and it is necessary to identify GC prognosis biomarkers

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