• Integrated system biology investigation (in-silico) of Co-expression of the lncRNAs and mRNAs associated and multiple intracellular signaling Pathways, with the Cervical carcinoma
  • Mahdieh Bakhshayesh,1 Mansoureh Azadeh,2,*
    1. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran
    2. Zist Fanavari Novin Biotechnology Institute, Isfahan, Iran


  • Introduction: Cervical carcinoma is the second, most common cause of death and the most malignant reproductive disease seen among females worldwide[1][2][3]. Dysregulated genes identified in cervical cancer clinical samples may help develop prognostic markers and therapeutic targets[3]. The expression mRNAs microarray from Gene expression profiling in cervical cancer tissue was analyzed. A single local base-pairing interaction occurs between mRNAs, miRNA interaction analysis reveals that miRNAs regulate the expression of mRNA and lncRNA in an interaction axis, and we also demonstrate strong interactions between miRNAs and lncRNAs. CDKN2A is known to be an important tumor suppressor gene[4]. CDKN2A, FOS and CCNA2 may be related to the occurrence of cervical squamous cell carcinoma[1][2][5][6][7]. The FOS proteins have been implicated as cell proliferation, differentiation, and transformation regulators. In some cases, expression of the FOS gene has also been associated with apoptotic cell death[4]. The protein encoded by the CCNA2 function as a regulator of the cell cycle[4].
  • Methods: Gene expression profiling in cervical cancer tissue GEO2R and DAVID database with GSE127265 was examined. The genes with logFC > 3 & logFC < -3 are considered as the differentially expressed genes (DEGs) in this dataset. The adjusted p-value (adj. P. Value) < 0.05 is considered the statistical significance level. miRNAs were regained from DIANA tools Tar Base v.8 databases, followed by Interaction lncRNAs and mRNAs by lncRRisearch databases and lncHUB databases. The DIANA tools TarBase v.3 were used to analyze miRNA–mRNA interactions. The Pathway enrichment analysis was carried out using the online databases KEGG and Reactome. The expression of lncRNAs in different tissues has been examined by the lnCAR databases. comparing the expression of genes in different tissue by Gepia2 databases and the protein-protein interaction analysis by STRING online software.
  • Results: We found that CDKN2A, FOS and CCNA2 mRNAs had the highest expression changes (adj. P. Val<0.05) in cervical cancer. miRNA interaction analysis revealed that hsa-let-7b-5p could regulate the expression of CDKN2A, FOS and CCNA2 and Linc01566 lncRNA in cell line HELA from Cervix tissue in an interaction axis which indicates the existence of a complex network. Interaction analysis of CDKN2A, FOS and Linc01566 lncRNA illustrated have a single local base-pairing interaction (Energy = -22.25 kcal/mol) and (Energy = -12.34 kcal/mol). Besides, there are common pathways between CDKN2A, FOS and CCNA2 including Pathway in cancer, Human Tcell Leukemia Virus 1 Infection and Cell Cycle. Additionally, FOS is involved in the MAPK signaling pathway and CDKN2A plays an important role in the P53 signaling pathway that the MAPK and p53 signaling pathways lead to Apoptosis.
  • Conclusion: We identified the hub lncRNA-mRNA network involved in regulating various biological processes in cell line HELA from Cervix tissue. CDKN2A, FOS and CCNA2 mRNAs and also, Co-Expression Linc01566 lncRNA and hsa-let-7b-5p miRNA could be prognostic biomarkers in cervical cancer. Moreover, CDKN2A by using The Cell cycle and P53 signaling pathway, FOS with such an effect on MAPK signaling pathway/ Estrogen signaling pathway and CCNA2 Through a block of differentiation would be able to regulate the CELL proliferation in Pathway Cancer.
  • Keywords: cervical cancer, P53 signaling pathway, Apoptosis, CELL proliferation, complex network