MicroRNA-30a-5p suppresses proliferation, invasion and tumor growth of hepatocellular cancer cells via targeting FOXA1

Abstract

Abstract. Deregulation of microRNAs (miRs) has been observed in a variety of types of human cancer. Previously, miR-30a-5p has been demonstrated to exhibit a suppressive role in hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unclear. The present study aimed to elucidate the regulatory mechanism of miR-30a-5p in proliferation and invasion of HCC cells. Quantitative reverse transcription polymerase and western blotting were used to examine mRNA and protein expression of Forkhead box A1 (FOXA1). MTT and Transwell assays were performed to examine proliferation and invasion. Luciferase reporter assay was used to determine the association between miR-30a-5p and FOXA1. The data indicated that miR-30a-5p was significantly downregulated in HCC tissues compared with normal liver tissues. Furthermore, the level of miR-30a-5p was lower in HCC tissues with higher histological grade and advanced tumor stage compared with tissues with lower histological grade and tumor stage. Additionally, restoration of miR-30a-5p expression decreased the proliferation and invasion of HCC HepG2 and SMMC-7721 cells. FOXA1, a novel oncogene in HCC, was further identified as a target of miR-30a-5p. Furthermore, high expression of miR-30a-5p suppressed mRNA and protein expression of FOXA1, while overexpression of FOXA1 reversed the suppressive effect of miR-30a-5p on proliferation and invasion of HepG2 and SMMC-7721 cells. FOXA1 was markedly upregulated in HCC tissues compared with normal liver tissues, and its level was higher in HCC tissues with higher histological grade and advanced tumor stage. In addition, it was found that overexpression of miR-30a-5p significantly suppressed the tumor growth of HCC cells in nude mice. Taken together, the present study supports that miR-30a-5p inhibits the proliferation, invasion, and tumor growth of HCC cells, partly at least, by inhibition of FOXA1 expression, and therefore suggests that miR-30a-5p may serve as a potential candidate for HCC therapy.

miR‑30a‑5p inhibits the proliferation, migration and invasion of melanoma cells by targeting SOX4

“…The function of miR-30a-5p in other cancers has been widely investigated. MiR-30a-5p has been identified as a tumor suppressor in hepatocellular cancer (23), renal cell carcinoma (24), small cell lung cancer (25), upper tract urothelial carcinoma (26), gastric cancer (27) and breast tumor (28). Moreover, Wei et al (29) indicated that miR-30a-5p suppresses tumor metastasis of human colorectal cancer by targeting ITGB3.…”

A Two-Cohort RNA-seq Study Reveals Changes in Endometrial and Blood miRNome in Fertile and Infertile Women

“…Nevertheless, this miRNA could indirectly imply to the dysregulated physiological conditions resulting in implantation failure and serves as a potential minimally invasive biomarker in this regard. miR-30a-5p acts as a tumour suppressor by inhibiting cell proliferation and invasion [61,62,63]. In blood cells, miR-30a takes part in the regulation of erythrocyte maturation [64].…”

Signification of forkhead box A1 (FOXA1) expression in thyroid cancers

“…Therefore, the authors claimed that miR-132 acts as a tumor suppressor targeting FOXA1 in thyroid papillary carcinoma [23]. Similarly, in other human diseases, FOXA1 expression has been found to be inhibited by miR-30a-5p and miR-212 in hepatocellular carcinomas [24,25], by miR-212 in osteosarcomas [26], by miR-194 in non-small cell lung cancers [27], and by miR-431 in necrotizing enterocolitis [28]. The current study included only one case of undifferentiated sarcoma of the thyroid.…”