RNA-Sequencing Based microRNA Expression Signature of Colorectal Cancer: The Impact of Oncogenic Targets Regulated by miR-490-3p |
| |
Authors: | Yuto Hozaka Yoshiaki Kita Ryutaro Yasudome Takako Tanaka Masumi Wada Tetsuya Idichi Kan Tanabe Shunichi Asai Shogo Moriya Hiroko Toda Shinichiro Mori Hiroshi Kurahara Takao Ohtsuka Naohiko Seki |
| |
Affiliation: | 1.Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan; (Y.H.); (Y.K.); (R.Y.); (T.T.); (M.W.); (T.I.); (K.T.); (H.T.); (S.M.); (H.K.); (T.O.);2.Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan;3.Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan; |
| |
Abstract: | To elucidate novel aspects of the molecular pathogenesis of colorectal cancer (CRC), we have created a new microRNA (miRNA) expression signature based on RNA-sequencing. Analysis of the signature showed that 84 miRNAs were upregulated, and 70 were downregulated in CRC tissues. Interestingly, our signature indicated that both guide and passenger strands of some miRNAs were significantly dysregulated in CRC tissues. These findings support our earlier data demonstrating the involvement of miRNA passenger strands in cancer pathogenesis. Our study focused on downregulated miR-490-3p and investigated its tumor-suppressive function in CRC cells. We successfully identified a total of 38 putative oncogenic targets regulated by miR-490-3p in CRC cells. Among these targets, the expression of three genes (IRAK1: p = 0.0427, FUT1: p = 0.0468, and GPRIN2: p = 0.0080) significantly predicted 5-year overall survival of CRC patients. Moreover, we analyzed the direct regulation of IRAK1 by miR-490-3p, and its resultant oncogenic function in CRC cells. Thus, we have clarified a part of the molecular pathway of CRC based on the action of tumor-suppressive miR-490-3p. This new miRNA expression signature of CRC will be a useful tool for elucidating new molecular pathogenesis in this disease. |
| |
Keywords: | microRNA colorectal cancer RNA-sequencing expression signature tumor-suppressor miR-490-3p IRAK1 |
|
|