STUDY OF RELATION BETWEEN MIR-210 AND p53 IN CANCER

INTRODUCTION AND OBJECTIVES: Cancer is one of the major public health problems in Brazil. p53 pathway is a central pathway in response to DNA damage and its deregulation is associated with tumorigenesis in more than 50% of tumor’ types. In addition, microRNAs are small non-coding RNAs that regulate gene expression posttranscriptionally by inhibiting translation of target mRNAs. miR-210 expression deregulation has been associated with cancer treatment resistance. Our group demonstrated that the inhibition of miR-210 associated with radiotherapy reduces cellular viability in glioblastoma cell lines with wildtype TP53. Thus, this work aims to evaluate whether there is a correlation between the expression of miR-210 and TP53 mutational status in different solid tumors, in vitro and in silico. MATERIAL AND METHODS: miR-210 expression was compared between tumor and non-tumor tissues, TP53 wildtype and mutated samples, and evaluated in disease staging and in nodal metastasis cases, in silico. Cell lines from breast, lung, esophagus cancer and glioblastoma with different TP53 mutational status were used to evaluate miR-210 expression by RT-qPCR and p53 protein levels by Western blotting. RESULTS AND CONCLUSION: In silico analysis revealed a higher expression of miR-210 in tumor tissues when compared to non-tumor tissues in breast, prostate, esophageal, lung and cervical squamous cell carcinoma. Corroborating this data, samples derived from different disease stages and nodal metastasis showed higher expression of miR-210 compared to non-tumor tissue. Additionally, we observed a higher expression of miR-210 in samples with mutated TP53 compared to samples with wild-type TP53 in breast cancer, prostate and lung adenocarcinoma. Only in prostate cancer we observed a poor overall survival in cases with high expression of miR-210. There was a higher expression of miR-210 in breast cancer and glioblastoma cell lines with TP53 mutation, corroborating the data of in silico analysis. However, there was a lower expression of miR-210 in lung cancer cell lines with TP53 mutation when compared to cell lines with wild type TP53. The esophageal cancer cell line with a thermosensitive mutation in TP53 did not show a significant difference in microRNA expression neither in p53 protein levels when cultivated at 32°C or at 37°C. Therefore, miR-210 is overexpressed in breast, prostate, esophageal, lung and cervical squamous cell carcinoma, however high expression is associated with worse survival only in prostate cancer. miR-210 appears to be associated with the presence of a TP53 mutation in breast and lung cancer in silico and in glioblastoma in vitro. In lung cancer cell lines, the inverse relation was observed for miR-210 expression and TP53 mutation.