miR-940 Suppresses Tumor Cell Invasion and Migration via Regulation of CXCR2 in Hepatocellular Carcinoma

Abstract

Aim. To investigate the expression of miR-940 in the hepatocellular carcinoma (HCC) and its impact on function and biological mechanism in the HCC cells. Methods. Quantitative RT-PCR analysis was used to quantify miR-940 expression in 46 cases of tissues and cells. Transfection of HCC cell lines was performed by miR-940 mimics; the abilities of invasion and migration were assessed through Transwell array. Western blot represents the alteration in expression of CXCR2 by miR-940 mimics. Results. miR-940 expression was decreased significantly in the HCC tissues and the relevant cell lines. miR-940 upregulation suppressed the invasion and migration of HCC cells in vitro. Furthermore, the CXCR2 was downregulated to suppress invasion and migration after miR-940 mimics. Moreover, decreased miR-940 expression was negatively correlated with Edmondson grade (P = 0.008), tumor microsatellite or multiple tumors (P = 0.04), vascular invasion (P = 0.035), and recurrence and metastasis (P = 0.038). Kaplan-Meier analysis demonstrated that decreased miR-940 expression contributed to poor overall survival (P < 0.05). Conclusions. Our findings present that miR-940 acts as a pivotal adaptor of CXCR2 and its transcription downregulated CXCR2 expression to decrease HCC invasion and migration in vitro. Our study suggests that miR-940 may be a novel poor prognostic biomarker for HCC.

Upregulation of histamine receptor H1 promotes tumor progression and contributes to poor prognosis in hepatocellular carcinoma

“…Rajendiran et al have reported that miR-940 is downregulated significantly in prostate cancer and suppresses cell migration and invasion [38]. In HCC, miR-940 was also found to be significantly decreased in the HCC tissues and cell lines, and function as a tumor suppressor through inhibition of invasion and migration of HCC cells [39,40]. Consistently, our present study showed that miR-940 was involved in the overexpression of H1HR in HCC cells.…”

Exosomal miR-940 maintains SRC-mediated oncogenic activity in cancer cells: a possible role for exosomal disposal of tumor suppressor miRNAs

“…It was reported in many studies that miR-940 was highly expressed in normal tissues compared with tumors, and miR-940 was shown to inhibit the migratory and invasive potential of cancer cells by suppressing CXCR2 [59], MIEN1 [58], MyD88 [57], Nestin [56], and ZNF24 [54]. Moreover, the Estrogen-Related Receptor Gamma (ESRRG) was targeted by miR-940, and suppression of ESRRG inhibited hepatocellular carcinoma cell lines growth and induced cell apoptosis.…”

MicroRNA‑940 promotes cell proliferation and invasion of glioma by directly targeting Kruppel‑like factor�9

“…miR-940 was previously demonstrated to be aberrantly expressed in a number of types of human cancer. miR-940 was downregulated in hepatocellular carcinoma, and this downregulation was significantly associated with Edmondson grade, tumor microsatellite or multiple tumors, vascular invasion, recurrence and metastasis (18,24). Patients with hepatocellular carcinoma and low miR-940 expression levels exhibited poorer prognosis compared with high expression levels (18).…”

“…MicroRNAs (miRNAs) comprise a series of endogenous, short single-stranded non-coding RNAs (19)(20)(21)(22)(23)(24)(25) molecules) that primarily serve as gene regulators (8). These molecules negatively regulate gene expression by directly binding to partial complimentary sites in the 3'-untranslated regions (3'-UTRs) of their target genes, resulting in mRNA degradation or inhibition of translation (9).…”