MiR-219-5p inhibits growth and metastasis of ovarian cancer cells by targeting HMGA2

Abstract

BackgroundAccumulating studies have demonstrated that high-mobility group A2 (HMGA2), an oncofetal protein, plays a role in tumor development and progression. However, the molecular role of HMGA2 in ovarian carcinoma is yet to be established. MicroRNAs (miRNAs), a group of small noncoding RNAs, negatively regulate gene expression and their dysregulation has been implicated in tumorigenesis. The aim of this study was to investigate the potential involvement of a specific miRNA, miR-219-5p, in HMGA2-induced ovarian cancer.MethodsThe ovarian cancer cell line, SKOV3, was employed, and miR-219-5p and HMGA2 overexpression vectors constructed. The CCK-8 kit was used to determine cell proliferation and the Transwell® assay used to measure cell invasion and migration. RT-PCR and western blot analyses were applied to analyze the expression of miR-219-5p and HMGA2, and the luciferase reporter assay used to examine the interactions between miR-219-5p and HMGA2. Nude mice were employed to characterize in vivo tumor growth regulation.ResultsExpression of miR-219-5p led to suppression of proliferation, invasion and migration of the ovarian cancer cell line, SKOV3, by targeting HMGA2. The inhibitory effects of miR-219-5p were reversed upon overexpression of HMGA2. Data from the luciferase reporter assay showed that miR-219-5p downregulates HMGA2 via direct integration with its 3′-UTR. Consistent with in vitro findings, expression of miR-219-5p led to significant inhibition of tumor growth in vivo.ConclusionOur results collectively suggest that miR-219-5p inhibits tumor growth and metastasis by targeting HMGA2.

Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer

“…In HUVECs, transmembrane glycoprotein neuropilin-1 increases DDAH1 expression, mediated by a post-transcriptional mechanism involving miR-219-5p (220). Although this regulation has not been assessed in cancer, miR-219-5p has been reported to have a tumor suppressive role in colon cancer (221,222) and ovarian cancer (223), which may in part relate to regulation of DDAH1.…”

LINC00461 Promoted Endometrial Carcinoma Growth and Migration by Targeting MicroRNA-219-5p/Cyclooxygenase-2 Signaling Axis

“…miR-219-5p is the only miRNA that was predicted to target COX-2 in EC so far. Moreover, several tumor-associated genes have been reported to be targeted by miR-219-5p in other types of cancers, including high-mobility group A2 in ovarian cancer 20 , platelet-derived growth factor receptor and calcyphosin in colorectal cancer 41 , 42 , and cadherin 1 and glypican-3 in HCC 22 , 43 . Due to miRNA’s characteristics of multiple targets, we further investigated whether miR-219-5p could negatively regulate these genes in EC.…”

“…Recently, microRNA-219-5p (miR-219-5p) was reported to attenuate an anti-inflammatory molecule resolvin D1-mediated obesity-induced nonalcoholic steatohepatitis 19 . Interestingly, miR-219-5p has been reported to be abnormally expressed in many types of cancers, such as ovarian cancer 20 , malignant melanoma 21 , etc. Increased miR-219-5p level was also observed in HCC, which promoted cell proliferation and migration of HCC cells by regulating CDH1 22 .…”

Long Non-coding RNA Colon Cancer-Associated Transcript-1 Promotes Migration, Invasion, and Epithelial Mesenchymal Transition of Lung Adenocarcinoma by Suppressing miR-219-1

“…A previous study observed that knockdown of CCAT1 induced a marked reduction in fibronectin and vimentin but upregulated E-cadherin, thereby restoring the epithelial phenotype of H1975 cells, which failed to consider the underlying mechanism of the effects of CCAT1 on EMT (Luo et al, 2014). miR-219 is increasingly recognized as a tumor suppressor in gastric cancer (Li Y. et al, 2019), hepatocellular carcinoma (Gong et al, 2019), and ovarian cancer (Xing et al, 2018). The role of miR-219-1 in LAD was unclear.…”