microRNA-489 Plays an Anti-Metastatic Role in Human Hepatocellular Carcinoma by Targeting Matrix Metalloproteinase-7

Abstract

Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of hepatocellular carcinoma (HCC). miR-489 was found to play either oncogenic or tumor suppressive roles in human cancers. Recent study reported that the levels of miR-489 in late recurrent HCC patients were evidently higher than that in early recurrent cases, suggesting that miR-489 may function as a tumor suppressive miRNA in HCC. Yet, the clinical value and biological function of miR-489 remain rarely known in HCC. Here, we presented that miR-489 level in HCC tissues was notably reduced compared to matched non-cancerous specimens. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of HCC patients. Accordingly, the levels of miR-489 were obviously down-regulated in HCC cells. Ectopic expression of miR-489 in HCCLM3 and MHCC97H cells prominently inhibits the migration and invasion of tumor cells and reduced lung metastases in vivo, while miR-489 knockdown increased these behaviors of HepG2 and MHCC97L cells. Mechanically, miR-489 negatively regulated matrix metalloproteinase-7 (MMP7) abundance in HCC cells. Herein, MMP7 was found to be a downstream molecule of miR-489 in HCC. An inversely correlation between miR-489 and MMP7 was confirmed in HCC specimens. MMP7 knockdown prohibited cell migration and invasion while MMP7 overexpression showed opposite effects on HCC cells. Furthermore, restoration of MMP7 expression could abrogate the anti-metastatic effects of miR-489 on HCCLM3 cells with enhanced cell migration and invasion. Altogether, miR-489 potentially acts as a prognostic predictor and a drug-target for HCC patients.

Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma

“…Second, Lionel Remy et al reported that MMP7 promotes colon carcinoma cell migration via cleavage of the laminin-5 beta3 chain [13]. Additionally, MMP7 was reported as a target gene of the WNT/β-catenin signaling pathway in many carcinomas [39][40][41], and micro489 [42], state3 [14], and cox-2 [43] were reported as upstream genes of MMP7 in the cooperative function of regulatory carcinomas. Regrettably, the mechanism underlying how MMP7 promotes the proliferation, metastasis and invasion of tongue squamous cell carcinoma was not revealed, although we demonstrated that MMP7 acts as oncogene in TSCC, a finding that will push us to research further.…”

<p>miR-489-3p Inhibits Prostate Cancer Progression by Targeting DLX1</p>

“…27 In addition, miR-489-3p exhibits anti-metastatic activity in human hepatocellular carcinoma by targeting MMP7. 28 MiR-489-3p also inhibits growth and invasion by targeting HDAC7 in colorectal cancer. 29 Thus, miR-489-3p may exert antitumor activity via the regulation of not only DLX1 but also other oncogenes.…”

Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in�vitro and in�vivo

“…miRNAs have been recognized as a new class of genes involved in human cancer and have recently been shown to be biomarkers of diagnostic, prognostic and therapeutic (10,11). Several studies have identified some miRNAs that were significantly altered and have the potential to restrain proliferation of cervical cancer (12,13).…”