The tumor suppressor protein p53 is intricately regulated by various signaling molecules, including the non-coding small RNAs, called the microRNAs (miRNAs). The in-silico analysis and the inverse expression status in the various cell lines raised the possibility of miR-27a being a new regulator of the p53. Using luciferase reporter assay and various mutational and functional analysis, we identified two putative binding sites of the miR-27a on the 3`UTR of the p53. The overexpression of the miR-27a in the human colorectal cancer cell line HCT-116+/+, resulted in the decreased expression of the endogenous p53 protein levels. During hypoxia of the HCT-116+/+ cells, the p53 showed increased accumulation after 3 hours and the levels were significantly up regulated till 24 hours of the hypoxia. The p53 expression dynamics during the hypoxia of the HCT-116+/+ cells were found inversely regulated by the miR-27a expression. Moreover, using cell viability assay, we established that after 3 hours of hypoxia, the accumulation of the p53 results in the decreased number of the viable HCT-116+/+ cells and the overexpression of the miR-27a resulted in the increased number of the viable HCT-116+/+ cells with concomitant decrease in the p53 expression. Additionally, our data indicated that the miR-27a and the p53 depict inverse expression dynamics in the 50% of the human colorectal cancer samples studied, as compared to the adjacent normal samples. Our data established that the miR-27a and the tumor suppressor protein p53 are part of the same signaling network that has important implications during hypoxia and tumorogenesis.
- Tumor suppressor protein
- colorectal cancer
- ©2016 The Author(s)
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