Identification of targets of miR-1 in OSCC
Head and neck squamous cell carcinoma (HNSCC), being the sixth most common neoplasm, is a significant cause of cancer morbidity and mortality over the globe. Oral Squamous Cell Carcinoma that comprises a major part of HNSCC accounts for about 90% of all oral malignancies. Smoking, chewing tobacco, alcohol consumption, infection by Human Papilloma Virus and other oral habits have been reported to be the major contributing factors. Approximately 6,30,000 people are diagnosed with and nearly 3,50,000 people are dying of OSCC annually and so it has become a worldwide matter of concern. There are various methods of gene regulation in the cancer pathogenesis pathway. One of the major pathways of post-transcriptional gene regulation is mediated by microRNAs (miRNAs). miRNAs are 22 nucleotides short non-coding RNAs which are involved in post-transcriptional gene regulation by binding with the 3’UTR of the target messengerRNAs (mRNAs) resulting in translational repression or mRNA cleavege. The recent advances in research identified de-regulation of several miRNAs in cancer. The previous studies of our laboratory identified microRNA-1(miR-1) as one of the down-regulated miRNAs in OSCC by small RNA sequencing and quantitative real-time PCR analysis. Hence, in the present study, we wanted to identify the targets of miR-1 and study its role in cancer biogenesis. The targets of miR-1 were predicted bioinformatically and validated by qPCR. Three genes were found to be downregulated in the SCC131_miR-1 cell line, which constitutively over expresses miR-1, as compared to the wildtype cell line, SCC131_WT. Moreover, functional characterization showed a decrease in migration and proliferation on miR-1 over expression. Hence, miR-1 mediates its tumor supressor action by targetting downstream oncogenic mRNAs thus inhibiting tumorigenesis.
Keywords: carcinoma, miRNA, mRNA, tumorigenesis