Identification and interaction analysis of hub genes and microRNA in hepatocellular carcinoma: using integrated bioinformatics analysis

Identification and interaction analysis of hub genes and microRNA in hepatocellular carcinoma: using integrated bioinformatics analysis
Keivan ardeshiri,¹ Shadi Omidghaemi,² Mohammad Rezaei,³ Anasik Karabedianhajiabadi,⁴ kolsoum saeidi,⁵ Mansoureh Azadeh,^6,*
1. Zist Fanavari Novin biotechnology institute, Isfahan, Iran
2. Zist Fanavari Novin biotechnology institute, Isfahan, Iran
3. Zist Fanavari Novin biotechnology institute, Isfahan, Iran
4. Zist Fanavari Novin biotechnology institute, Isfahan, Iran
5. Student Research Committee, School of Medicine , Kerman University of Medical Sciences, Kerman , Iran
6. Zist Fanavari Novin biotechnology institute, Isfahan
Introduction: Hepatocellular carcinoma is considered about 90% of liver cancers, which is being caused by hepatitis B and C viruses named HBV and HCV respectively. During the last decades’ researches, the molecular mechanisms of HCC is still under study. Based on the latest studies, different risk factors could trigger HCC, which among them the genetic biomarkers such as miRNAs (small non-coding RNAs) are considered to have essential impact on HCC progression. Thus, a wide range of bioinformatics analysis have been used for the recognition of these biomarkers as promising targets for the diagnosis and treatment of HCC.
Methods: Initially, NCBI Gene Expression Omnibus (GEO) has been chosen to get the essential GSE, which this gene expression profile has been downloaded and analyzed by R studio in order to find the genes which have notable up and down expression regulations, that by analyzation of genes’ pathways, RRM2 has been selected. Moreover, miRWalk and miRTarBase databases have been used to identify numerous target microRNAs of RRM2. The binding and paring scores of these microRNAs have been studied which the interaction of them have been showed as a Cystoscope software (3.8.0). Eventually, the analyzation of the pathways involved in HCC, the required microRNA has been selected.
Results: Based on GEO analysis total number of 2 GSEs were indicated among HCC and cirrhotic tissues. This analysis outcomes assigned that the GSE112790 and GSE121248 were surprisingly enriched in several biological mechanisms. A total number of 29 up-regulated and 100 down-regulated genes from both GSEs were indicated which by DAVID database the pathways of each were examined separately. Up-regulated genes pointed HCC-related pathways named, cell cycle and p53 signaling pathways that RRM2 demonstrated as a vital gene of these pathways. Moreover, 100 DEGs were revealed to be included in both pathways with significant downregulation of expression.
Conclusion: According to the all mentioned events, concluded that hsa-miR-34a-5p via inhibition of RRM2 gene’s function, an essential gene for cell growth, acts as tumor suppressor in p53 signaling pathway of HCC. Thus, these findings could provide a promising therapy method for treatment of HCC patients.
Keywords: Liver disease, Hepatocellular carcinoma, Bioinformatics, miRNA, pathway