Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma

Abstract

The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (≤ 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo. Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC.

The Clinical and Theranostic Values of Activated Leukocyte Cell Adhesion Molecule (ALCAM)/CD166 in Human Solid Cancers

“…ALCAM expression can also be regulated by microRNAs. For example, microRNA-192, miR-148b-3p, miR-152, and miR-483-5p have been shown to be able to suppress the expression of ALCAM in tumour cells, including gastric, pituitary, and liver cancer cells, possibly by targeting the 3 -UTR binding site of the transcription region of ALCAM gene [19][20][21][22].…”

microRNAs Orchestrate Pathophysiology of Breast Cancer Brain Metastasis: Advances in Therapy

“…MiR-126 and miR-1185 regulate endothelial expression of VCAM1 [63,108]. ALCAM is reported as a target gene of miR-483-5p [64].…”

<p>miR-135b-5p Suppresses Androgen Receptor-Enhanced Hepatocellular Carcinoma Cell Proliferation via Regulating the HIF-2α/c-Myc/P27 Signals in vitro</p>

“…Growing evidence indicates that the deregulation of miRNAs occurs in HCC progression 29 and recent studies have further developed the miRNA-based risk of HCC recurrence following liver resection. 30 Results of miRNA therapies in HCC showed that either reintroducing suppressor miRNAs or inhibiting oncogenic miRNAs suppress HCC progression in various HCC cell lines in vitro, animal models in vivo, and human clinical trials. 31 Our work provides additional details, identifying a specific miRNA and its target gene, which are involved in the regulation of HCC proliferation.…”