Identification of Novel Cancer Biomarkers in LIHC

LIHC (Liver Hepatocellular Carcinoma) is the most common malignant cancer around world. Recent studies reported that miRNA plays vital roles in tumor development and progression, suggesting the miRNA in LIHC could been regarded as potential prognostic biomarkers. Assessment of the up-regulated miRNA and its target protein as novel cancer biomarkers in LIHC cancer cells. First, we assessed the up-regulated and down-regulated miRNA in LIHC and normal tissue from The Cancer Genome Atlas (TCGA) database. Next, we performed the survival plot and time ROC plot to select the LIHC related miRNA. Then, by introduction of TargetScan Human software and TCGA database, we got the miRNA related proteins. Lastly, by series of cell biology and biochemistry assays, we illustrated miRNA targeted proteins could affect cancer cell physiological function. Identification of miR-10b-5p, miR-224-5-p, miR-183-5p, miR-182-5p, miR-217, miR-196b-5p, miR-452-5p and miR-9-5p are overexpressed in LIHC than in normal tissue. The elevated expression of miR-452-5p and miR-9-5p are associated with significantly poorer over survival of LIHC patients, miR-9-5p and miR-452-5p could restrict the expression of PDK4 and COLEC10 respectively, down-regulated level of PDK4 and COLEC10 are correlated with poorer over survival in LIHC patients. Moreover, overexpression of PDK4 and COLEC10 in LIHC cancer cells generated cell apoptosis and growth retardation, cell derived xenograft assay found the PDK4 and COLEC10 brought the development and progression retardation of LIHC. GO and KEGG analysis showed that PDK4 and COLEC10 positive correlation genes are involved in PPAR signaling pathway and PI3K−Akt signaling pathway. We found two new diagnostic markers in LIHC, miR-9-5p and miR-452-5p, which may facilitate the early diagnosis and treatment, we also uncovered that PDK4 and COLEC10 could been identified as tumor suppressors by misregulation of cell psychological function. In LIHC cancer cell, miR-9-5p and miR-452-5p acted as oncogene factors by directly suppress the expression of PDK4 and COLEC10.Activation of PPAR signaling pathway and PI3K-Akt signaling pathway may be viewed as potential therapeutic approach in LIHC.