Talk on Saturday 11:30-11:45am submitted by Sumirtha Balaratnam
piRNA mediated down regulation of ferritin heavy chain 1 mRNA in Triple Negative Breast Cancer cells
Sumirtha Balaratnam (Kent State University), Soumitra Basu (Kent State University)
The piwi interacting RNAs (piRNAs) are small non-coding RNAs mostly 24-32 nucleotides in length. The piRNAs are defined by their ability to specifically bind to the PIWI proteins, a requirement for their functions. The piRNAs are involved in germline development, transposons control, transcriptional and posttranscriptional gene regulation. However, piRNA mediated post-transciptional gene regulation in somatic cells is not well understood. We discovered a human piRNA (piR-FTH1) which has a complementary sequence in the ferritin heavy chain 1 (FTH1) mRNA. We demonstrate that piR-FTH1 expression is inversely correlated to the expression of FTH1 in most tumor cell lines. piR-FTH1 negatively regulates the FTH1 expression at posttranscriptional level in MDA-MB 231 cell lines. Further we confirmed that transfected piR-FTH1 knocks down the FTH1 mRNA through piR-FTH1-HIWI-RISC pathway by binding to HIWI2 and HILI. FTH1 repression by piR-FTH1 increased the chemotherapuetic agent Doxorubicin’s sensitivity by a remarkable 20 fold compared to the cell line treated with control siRNA sequence. Since most of the current piRNA mediated knockdown of target mRNA were only described in germ line cells, here we report piRNA mediated post transcriptional gene regulation in somatic cells. Thus, it will have a broader impact on treatment of various diseases that are linked to elevated level of specific mRNAs which have a piRNA target.
Keywords: piRNA, post-transcriptional regulation, Ferritin heavy chain 1