Roy, Jyoti (2014) Epigenetic regulation of key genes involved in Cervical malignancy. MSc thesis.
microRNAs (miRNAs) are single stranded non-coding RNAs of about 22 nucleotides that have been reported to be involved in various biological processes like embryonic development, cell proliferation, differentiation, apoptosis, developmental timing etc. The role of miRNAs as tumor suppressors/oncomiRs has been reported in many cancers. In this study, we performed genome-wide expression analysis of miRNAs as well as mRNAs in cervical cancer and obtained 257 up-regulated and 81 down-regulated mRNAs as well as 27 up-regulated & 14 down-regulated miRNAs. Enrichment analysis of differentially expressed mRNAs of cervical cancer revealed CYR61 (cysteine-rich, angiogenic inducer, 61) as a key gene involved in vascularisation of the tumors. This CYR61 was found to harbor target sites (7mer-m8) for hsa-miR-221 as inferred from TargetScan predictions. From qRT-PCR study in HeLa cell lines, we found that CYR61 is over-expressed, whereas hsa-miR-221 is down-regulated in cancer system. The altered expression of CYR61 might be due to down-regulation of hsa-miR-221 as this miRNA has target sites within 3/UTR of CYR61 which can be further confirmed by luciferase reporter assay. We hypothesize that hsa-miR-221 might be playing a role in metastatic spread and lethality in cervical cancer by altering the expression of the corresponding mRNA through RNA interference mechanism. Moreover, it can be expected that the altered expression of hsa-miR-221 may be due to promoter hypermethylation of the miRNA gene or through targeting by other non-coding RNAs, such as lncRNAs which need further studies in future.
|Thesis ( MSc)
|microRNAs, CYR61, angiogenesis, cervical cancer, metastasis, DNA methylation
|Life Science > Microbiology
|Sciences > Department of Life Science
|09 Sep 2014 16:15
|09 Sep 2014 16:15
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