Bioinformatics study on function of NKX3-1 gene and involved miRNAs through prostate cancer
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Milad Sheikh,1 Zeynab Khajavi,2 Pegah Javid,3 Mansoureh Azadeh,4,*
1. Zist-fanavari Novin Biotechnology Department, Provincial Technical and Vocational Training Organization
2. Zist-fanavari Novin Biotechnology Department, Provincial Technical and Vocational Training Organization
3. Zist-fanavari Novin Biotechnology Department, Provincial Technical and Vocational Training Organization
4. Zist-fanavari Novin Biotechnology Department, Provincial Technical and Vocational Training Organization
- Introduction: Prostate cancer is the second most frequent cancer in men and the fifth cause of death worldwide. The NK3 homeobox 1 (NKX3-1) is a prostate-specific tumor suppressor gene, which is located on chromosome 8p. The small non-coding RNAs (microRNAs) are involved in interaction with NKX3-1 gene. In this study, function of NKX3-1 in prostate cancer and the involved miRNAs in prostate cancer was investigated using bioinformatics databases.
- Methods: The expression analysis was done on GSE26910 chosen from Gene Expression Omnibus (GEO) datasets in order to find the tumor suppressor gene in prostate cancer while prostatic and normal samples were analyzed by GEO2R package. The GEPIA2 database obtained more information about NKX3-1 expression in normal and prostatic samples. The pathways involved in prostate cancer process was studied in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database. The interaction between miRNAs and NKX3-1 was detected by miRTargetLink 2.0. The DIANA TOOLS - mirPath v.3 was used to find the role of miRNAs in prostate cancer.
- Results: KEGG pathways revealed that, BCL-2-associated agonist of cell death (BAD) affects the process of apoptosis in prostate cancer pathway. The function of BAD is inhibited and apoptosis inhibition occurs when it is phosphorylated by protein kinase B (PKB/AKT). The inhibition of apoptosis, leads the cells to tumorigenesis. NKX3-1, a tumor suppressor gene, inhibits PKB/AKT activity indirectly and prevents the pathway toward cancer in phosphatidylinositol-3-kinase (PI3K) signaling pathway. The analyzed data showed that hsa-miR-155-5p and hsa-miR-92a-3p are correlated to NKX3-1 gene. The information obtained from miRPath v.3 showed that these miRNAs are involved in prostate cancer.
- Conclusion: NKX3-1 can inhibit apoptosis indirectly by its activity in PI3K signaling pathway as a tumor suppressor. Since NKX3-1 is a tumor suppressor gene, the associated miRNAs - hsa-miR-155-5p (with strong validation) and hsa-miR-92a-3p (with weak validation)- can play roles in prostatic cancer.
- Keywords: NKX3-1 gene; micro-RNA; PI3K pathway; Tumor suppressor
