Interactome analysis of gene expression profiles identifies CDC6 as a potential therapeutic target modified by miR-215-5p in hepatocellular carcinoma

Abstract

Background: Illustrating the pathogenesis of hepatocellular carcinoma (HCC) pathogenesis as well as identifying specific biomarkers are of great significance. Methods: The original CEL files were obtain from Gene Expression Omnibus, then affymetrix package was used to preprocess the CEL files, the function of DEGs were investigated by multiple bioinformatics approach. Finally, typical HCC cell lines and tissue samples were using to validate the role of CDC6 in vitro. Bioinformatics software was used to predict potential microRNA of CDC6. Luciferase assay was used to verify the interactions between CDC6 and microRNA. Results: A total of 445 DEGs were identified in HCC tissues based on two GEO datasets. GSEA results showed that the significant enriched gene sets were only associated with cell cycle signaling pathway. In the co-expression analysis, there were 370 hub genes from the blue modules were screened. We integrated DEGs, hub genes, TCGA cohort and GSEA analyses to further obtain 10 upregulated genes for validation. These genes were overexpressed in HCC tissues and negatively associated with overall and disease-free survival in HCC patients and related to immune cell infiltration in HCC microenvironments. Finally, Cell Division Cycle 6 (CDC6) was highlighted as one of the most probable genes among the 10 candidates participating in cancer process. The expression of CDC6 either in public datasets and HCC tissues sample were commonly high than the non-cancerous counterpart. Furthermore, we recognized that miR-215-5p, could directly bind to the 3'UTR of CDC6. In addition, CDC6 promoted proliferation via regulation of G1 phase checkpoint and was negative regulated by miR-215-5p to involve in the proliferation of HCC. Conclusion: Our study suggested that CDC6 served as a potential therapeutic target for HCC.

Identification of lncRNA/circRNA-miRNA-mRNA ceRNA Network as Biomarkers for Hepatocellular Carcinoma

“…In cancer cells, aberrant expression of CDC6 is involved in proliferation and tumor growth by modulating cell cycle ( Lim and Townsend, 2020 ). Xu et al revealed that CDC6 was regulated by miR-215-5p to involve in the proliferation of HCC ( Xu H et al, 2020 ). They also found that CDC6 was negatively associated with overall and disease-free survival in HCC patients.…”

Melatonin: A regulator of the interplay between FoxO1, miR96, and miR215 signaling to diminish the growth, survival, and metastasis of murine adenocarcinoma

“…supplementation was revealed via promoting P53‐ mitochondrial dependent apoptosis which is illustrated by P53 and Bax upregulation and marked downregulation of the antiapoptotic protein Bcl2. Interestingly, miR215 expression was found to be upregulated by P53 expression 41 . In addition, the effect of FoxO1 on stimulation of cell apoptosis via mitochondrial dependent pathway was recorded 40 .…”

“…Interestingly, miR215 expression was found to be upregulated by P53 expression. 41 In addition, the effect of FoxO1 on stimulation of cell apoptosis via mitochondrial dependent pathway was recorded. 40 When FoxO activity is compromised throughout the oxidative stress it becomes advantageous for cell survival.…”

Identification of critical genes and biological signaling for metformin treated liver cancer

“…The high expression of RRM2 was found in 81% of patients with liver cancer and the expression of RRM2 was associated with viral etiology and liver cirrhosis, which may be a biological marker for poor prognosis of liver cancer 35 . CDC6 was identified as a therapeutic target of miR-215 in liver cancer 36 . Moreover, CDC6 is an essential player for DNA replication, which is related to the risk for liver cancer 37 .…”