miR‑498 inhibits the growth and metastasis of liver cancer by targeting ZEB2

Abstract

MicroRNAs (miRNAs) play critical roles in the growth, metastasis and therapeutic resistance of liver cancer. Accumulating evidence suggests that miR-498 is aberrantly expressed in several human malignancies. However, the role and underlying mechanism of miR-498 in liver cancer remain unclear. In the present study, we investigated the potential roles and clinical value of miR-498 in liver cancer. We found that the miR-498 expression level was significantly lower in liver cancer patient tissues than that in healthy control tissues. The expression of miR-498 was also decreased in liver cancer cell lines compared to that noted in a normal human normal liver cell line. miR-498 overexpression markedly inhibited liver cancer cell proliferation, migration and invasion. miR-498 overexpression induced cell cycle arrest and apoptosis while it suppressed epithelial-mesenchymal transition (EMT) in liver cancer cells. Bioinformatic analysis and luciferase reporter assay further identified zinc finger E-box binding homeobox 2 (ZEB2) as a novel target of miR-498. Furthermore, ZEB2 knockdown recapitulated the inhibitory effects of miR-498 overexpression in liver cancer cells. ZEB2 overexpression rescued the inhibition of liver cancer cell proliferation, migration, and invasion by miR-498, indicating that ZEB2 acts as a downstream effector of miR-498 in liver cancer cells. Thus, we demonstrated that miR-498 suppresses the growth and metastasis of liver cancer cells, partly at least, by directly targeting ZEB2, suggesting that miR-498 may serve as a potential biomarker for the diagnosis and therapy of liver cancer.

<p>Upregulation Of miR-153 Inhibits Triple-Negative Breast Cancer Progression By Targeting ZEB2-Mediated EMT And Contributes To Better Prognosis</p>

“…One of the main functions of ZEB2 is to promote tumorigenesis and development by regulating EMT. Previous studies have confirmed that ZEB2 is related to infiltration and metastasis of multiple types of carcinomas, such as gastric malignancy, 36 liver malignant tumor 37 and non-small cell lung carcinoma. 38 In BC, Ang et al pointed out that the positive expression rates of ZEB2 mRNA and protein in ER-positive and ER-negative BC were different, but there was no significant statistical difference.…”

Downregulated lncRNA UCA1 acts as ceRNA to adsorb microRNA-498 to repress proliferation, invasion and epithelial mesenchymal transition of esophageal cancer cells by decreasing ZEB2 expression

“…miRNA-485-5p (miR-485-5p) strained EC tumorigenesis and could provide as a novel candidate for therapeutic applications in EC treatment [11]. MiR-498 has been verified to be one of the significant determinants of cell tumorigenicity in all kinds of tumors [12,13]. Zinc finger E-box-binding homeobox 2 (ZEB2) is structurally connected E-box binding homeobox transcription factors that induce epithelial mesenchymal transition (EMT) during development and disease [14].…”

miR-498 inhibits cell proliferation and metastasis by targeting FOXK1 in gastric cancer

“…The miRNAs mediate the cell survival, proliferation, apoptosis, tumor growth, and metastasis by acting as a regulators of genes expression [8] . It has been widely reported that miR-498 were involved in the regulation of various cancers and were considered to be the prognostic biomarker and therapeutic target for prostate cancer [9] , triple negative breast cancer [10] , esophageal squamous cell carcinoma [11] , liver cancer [12] and non-small cell lung cancer [13] . A previous study has found the overexpression miR-498 inhibits gastric cancer cell proliferation, migration and invasion and the long non-coding RNA UFC1 promotes gastric cancer progression by regulating miR-498/Lin28b [14] .…”