BICD1 functions as a prognostic biomarker and promotes hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is the most predominant type of primary liver cancer and has a high degree of malignancy as well as mortality rate. Many drivers are involved in the development and progression of HCC. A recent study has reported that high BICD cargo adaptor 1 (BICD1) expression indicates poor prognosis of glioblastoma. But, the expression and biological function of BICD1 in HCC remain unclear. In current study, we found that the expression of BICD1 was markedly up-regulated in HCC tissues compared to adjacent nontumor tissues. GEPIA dataset and GSE datasets were consistently indicated the elevated expression of BICD1 in HCC. Furthermore, BICD1 was highly expressed in HCC cell lines including Hep3B, Huh7, MHCC97H and HCCLM3 as compared with that in LO2 cells. High BICD1 expression was positively correlated with malignant clinical features, such as tumor size ≥ 5 cm, venous infiltration and advanced tumor stages. HCC patients highly expressing BICD1 showed a significant shorter overall survival compared to BICD1 low-expression cases. Moreover, TCGA-LIHC data further demonstrated that the up-regulated BICD1 expression predicted poor prognosis of HCC patients. Next, we revealed that BICD1 knockdown prominently suppressed the proliferation, migration and invasion of HCCLM3 cells. Conversely, ectopic expression of BICD1 remarkably facilitated these malignant behaviors of Hep3B cells. Interestingly, BICD1 knockdown abolished hypoxia-induced HCC cell proliferation, migration and invasion. In conclusion, we provide the first evidence to support that BICD1 functions as a predictor for the prognosis of HCC and may serve as a promising therapeutic target for further HCC treatment.

MicroRNA-519c-3p promotes tumor growth and metastasis of hepatocellular carcinoma by targeting BTG3.

Tumor recurrence and metastasis after surgical resection are the major causes for the cancer-related death of hepatocellular carcinoma (HCC). Thus, better understanding the mechanisms involved in tumor progression will benefit to improve HCC treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) play critical roles in the development and progression of HCC. However, the function of miR-519c-3p in HCC and its related mechanism remain unexplored. Here, we reported that miR-519c-3p was strongly overexpressed in HCC tissues, which was significantly correlated with poor prognosis and clinicopathological features including tumor size ≥5 cm, vascular invasion and advanced tumor-node-metastasis (TNM) stages (III + IV). Furthermore, the elevated levels of miR-519c-3p were observed in HCC cell lines. Subsequently, gain- or loss-of-function assays demonstrated that miR-519c-3p promoted HCC cell proliferation, migration as well as invasion in vitro, and facilitated the growth and metastasis of HCC cells in vivo. Mechanistically, B-cell translocation gene 3 (BTG3) was identified as a direct downstream target of miR-519c-3p. The level of BTG3 mRNA was downregulated in HCC and negatively correlated with miR-519c-3p expression. Western blotting confirmed that BTG3 was negatively regulated by miR-519c-3p in HCC cells. Luciferase reporter assays illustrated the direct interaction between miR-519c-3p and the 3'UTR of BTG3 mRNA. Recuse experiments demonstrated that BTG3 mediated the promoting effects of miR-519c-3p on the proliferation and motility of HCC cells. Collectively, our results suggest that miR-519c-3p functions as a tumor promotor in regulating the growth and metastasis of HCC by targeting BTG3, and potentially serves as a novel therapeutic target for HCC.

MicroRNA-1271 functions as a metastasis and epithelial-mesenchymal transition inhibitor in human HCC by targeting the PTP4A1/c-Src axis.

MicroRNAs (miRNAs or miRs) have been shown to regulate hepatocellular carcinoma (HCC) metastasis. In the present study, we focused on the functions of miR-1271 in HCC metastasis. The downregulation of miR-1271 was found to be associated with to venous infiltration, an advanced TNM stage (III+IV stage) and a shorter survival time. Our in vitro and in vivo data demonstrated that miR-1271 prevented HCC cell migration and invasion, as well as the formation of lung metastatic clusters. In addition, miR-1271 was demonstrated to markedly inhibit the epithelial-mesenchymal transition (EMT) of HCC cells. Importantly, protein tyrosine phosphatase type IVA member 1 (PTP4A1) was identified as a direct downstream target of miR-1271 in HCC. Furthermore, we confirmed that the phosphorylation of c-Src at Tyr416 mediated by PTP4A1 was a potential anti-HCC mechanism of action of miR-1271. On the whole, our data indicate that miR-1271 inhibits HCC metastasis by targeting the PTP4A1/c-Src signaling pathway and may serve as a prospective cancer therapeutic target for HCC.