LncRNA MCM3AP-AS1 Regulates Epidermal Growth Factor Receptor and Autophagy to Promote Hepatocellular Carcinoma Metastasis by Interacting with miR-455.

Hepatocellular carcinoma (HCC) has been reported to be one of the major tumors in the world. There is a study indicating that MCM3AP-AS1 is an oncogenic factor in HCC; however, the mechanism by which MCM3AP-AS1 regulates HCC remains not fully understood. Reverse Transcription-quantitative PCR and Western blot approaches were used to detect mRNA and protein levels of various genes. To examine invasion of HCC cells and lymphatic vessel formation of human dermal lymphatic endothelial cells (HDLECs), we employed transwell invasion assay and lymphatic vessel assay. Bioinformatic analysis and luciferase reporter assay were used to establish direct interactions between MCM3AP-AS1 and miR-455. Besides, The Cancer Genome Atlas analyses of HCCs were performed to determine the association of MCM3AP-AS1 and epidermal growth factor receptor (EGFR) with overall survival. MCM3AP-AS1 knockdown impaired invasion of HCC cells and lymphatic vessel formation of HDLECs. MCM3AP-AS1 directly interacted with miR-455. Furthermore, miR-455 inhibitor-transfected HepG2 cells enhanced the invasion and lymphatic vessel formation abilities. The rescue experiments indicated that EGFR was critical for MCM3AP-AS1- and miR-455-regulated invasion and lymphatic vessel formation. More interestingly, autophagy-related genes (Beclin1, LC3 II/I, and ATG7) were abnormally regulated in miR-455 mimic or inhibitor HepG2 cells. miR-455 mimic inhibited cell invasion and lymphatic vessel formation, which was evidently abrogated by ATG7 overexpression. Finally, we analyzed The Cancer Genome Atlas data sets to test the upregulated expression levels of MCM3AP-AS1 and EGFR. In addition, the results showed that low levels of both genes facilitate survival of HCC patients. In this study, we reveal a novel mechanism underlying MCM3AP-AS1-induced HCC metastasis by regulating miR-455. The conclusions provide more insights into understanding mechanism underlying HCC and help development of therapeutical approaches for treating HCC.