Down-regulation of DLG2 predicts an unfavorable prognosis and promotes the proliferation and migration of Hepatocellular Carcinoma.
Abstract Background Discs large MAGUK scaffold protein 2 (DLG2), a member of the MAGUK family, has been associated with certain tumor suppressing processes. In this study, we aim to identify the prognosis value and specific function of DLG2 in hepatocellular carcinomas (HCCs). Methods Expression of DLG2 in HCCs and adjacent normal tissues (NTs) was analyzed with transcriptomic datasets from the Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) and immunohistochemical (IHC) staining of a tissue microarray (TMA). Prognostic roles of DLG2 in HCCs were investigated in the TMA cohort and validated in two cohorts from HCCDB. The in vitro activities of DLG2 were investigated in cultured HCC cells with lentiviruses. The underlying mechanism was explored using Gene Set Enrichment Analysis (GSEA) and gene-gene correlation analyses with The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) dataset. Results The expression of DLG2 was significantly decreased in HCCs compared to that in NTs. Down-regulation of DLG2 in HCCs was associated with unfavorable prognosis. Overexpression of DLG2 inhibited, while knockdown of DLG2 prompted proliferation and migration of cultured HCCs. Mechanistically, DLG2 may inhibited cell growth of HCCs by interacting with key molecules that regulate cell cycles. Conclusion DLG2 inhibited HCC progression and may be a novel prognosis biomarker and therapeutic target for HCC.