MYC-Micro RNA-Transcript Regulatory Crosstalks in STS Oncogenesis

Abstract

MicroRNAs (miRNA) are a family of small non-coding RNAs (ncRNAs) having capability of regulating gene expression at the post-transcriptional level. MicroRNAs are reported to have role in various biological processes like development of embryo, cell proliferation, differentiation of cells into other forms, cell death, developmental timing, etc. The role of miRNAs as tumor suppressors/oncomiR has already been reported in many cancers. These ncRNAs can alter cellular metabolism by directly interacting with target gene transcripts. Therefore, miRNA profiling is used for detection and progression of cancer in various field of cancer biology such as proliferation, programmed cell death, cancer cell migration and angiogenesis. Our study is mainly based on identification of novel differentially expressed targets of MYC regulated miRNAs that are suspected to play role in fibrosarcoma from microarray data analysis followed by qRT-PCR for experimental validation of selected pair of mRNA (COL1A2 and RRM2). From qRT-PCR study in HT-1080 cell lines, we found that COL1A2 and RRM2 are over-expressed in cancer system and their targeting miRNAs are down-regulated. The altered expression of COL1A2 and RRM2 might be due to down regulation of hsa-let-7g and hsa-let-7b as these miRNAs have target sites within 3/UTR of COL1A2 and RRM2. We can assume that these target genes and their miRNAs might be playing a role in metastatic in STS by altering the expression of the corresponding mRNA through RNA interference mechanism, which can be a probable therapeutic target in fibrosarcoma.