MicroRNA-320a Promotes Epithelial Ovarian Cancer Cell Proliferation and Invasion by Targeting RASSF8.

Lili Zhang,Aihua Li,Aifeng Zhang,Fengxi He,Anqi Zhang,Huixiao Chen,Shiqian Zhang

doi:10.3389/fonc.2021.581932

Abstract

MicroRNAs (miRNAs) play important roles in tumorigenesis by controlling target gene expression. With opposing roles as a tumor suppressor or oncogene, microRNA-320a (miR-320a) was found to participate in tumor genesis and progression and also identified as a potentially useful marker in cancer diagnosis, treatment, and prognosis. To better understand the role of miR-320a in ovarian cancer, we investigated miR-320a expression in epithelial ovarian cancer (EOC) specimens as well as EOC cell lines and analyzed correlations between miR-320a expression and processes associated with EOC progression. The miR-320a level in EOC specimens was found to be associated with ovarian cancer progression and infiltration. Through in vitro and in vivo studies, we found that miR-320a significantly promoted the proliferation, migration, and invasion of EOC cells, and we identified RASSF8 as a target gene of miR-320a that was downregulated in EOC tissues and cell lines. In vitro downregulation of RASSF8 promoted the growth, migration, and invasion of EOC cells. Together these findings indicate that RASSF8 is a direct target of miR-320a, through which miR-320a promotes the progression of EOC.

Highlights

Epithelial ovarian cancer (EOC) is the most lethal subtype of this gynecologic malignancy [1], with a 5-year survival rate of approximately 35–40% [2]
MiR-320a Is Upregulated in Ovarian Cancer Samples and Cell Lines miR-320a expression levels in 20 pairs of EOC tissues and adjacent normal ovarian tissues, in three ovarian cancer cell lines, and in a normal ovarian epithelial cell line were determined by qRT-PCR
EOC is a major cause of tumor-related death in females, and in research related to EOC progression and metastasis, some miRNAs have been shown to be oncogenic while others were shown to have suppressive functions [9, 14,15,16]

Summary

Introduction

Epithelial ovarian cancer (EOC) is the most lethal subtype of this gynecologic malignancy [1], with a 5-year survival rate of approximately 35–40% [2]. Some miRNAs represent potential therapeutic targets for cancer management. MiRNAs are a class of small, non-coding RNAs (18–22 nt in length) that bind to the 3’-untranslated regions (3’-UTRs) of the mRNAs of target genes, resulting in mRNA degradation and thereby regulating target gene expression [4]. Prior research has shown altered expression of miR-320a in various cancers, such as salivary adenoid cystic carcinoma [5], colon cancer [6], gastric cancer [7] and breast cancer [8]. The potential role of miR-320a in EOC remained to be determined. By analyzing ovarian cancer-related data from the Gene Expression Omnibus (GEO), Carcinogenicity of miR-320 in EOC

Methods

Results

Conclusion