Background: Activation of IGF-1/IGF-1R signaling cascade is a hallmark in Hepatocellular carcinoma (HCC). In our previous work, we showed that miR-486-5p acts as a tumor suppressor miRNA in HCC mainly by vertically blocking IGF-1/IGF-1R axis and its downstream signaling mediators STAT3, mTOR and c-Myc. Recently, it was reported that the proto-oncogene c-Myc directly down-regulates the tumor suppressor miRNA, let-7a, especially in HCC and that let-7 directly targets the oncogenic RNA binding protein IGF2BP1. Aim: Therefore, the main aim of this study was to investigate the indirect interplay between microRNAs; miR-486-5p and miR-let- 7a through c-MYC thereby its effect on a vital member of IGF-axis, IGF2BP1, in HCC. Methods: Huh-7 cell lines were cultured and transfected using miR-486-5p mimics using lipofection technique. Forty-eight hours post transfection, total RNA was extracted, reverse transcribed into cDNA, and finally amplified and quantified using q-RT-PCR. Impact of miR-486-5p on cell cycle was assessed using cell cycle vectors carrying response elements for the cell cycle protein c-Myc. Results: Efficient delivery of miR-486-5p in Huh-7 cells was obtained, where mimicked cells showed more than 8000 folds increase in miR-486-5p expression level. Ectopic expression of miR- 486-5p in Huh-7 cells resulted in a significant decrease in c-Myc protein expression, an increase in the expression level of the tumor suppressor, let-7a and finally forcing the expression of miR-486-5p showed a significant repression of the oncogenic validated target of let-7a, IGF2BP1. Conclusions: This study shows a novel mechanism of action of the tumor suppressor miR-486-5p. MiR-486-5p was found to indirectly repress an essential member of IGF-axis, the oncogenic RNA binding protein IGF2BP1, mainly through decreasing c-MYC expression and up regulating let-7a expression.
Comments: 4 Pages.
[v1] 2017-08-23 06:21:38
Unique-IP document downloads: 20 times
Vixra.org is a pre-print repository rather than a journal. Articles hosted may not yet have been verified by peer-review and should be treated as preliminary. In particular, anything that appears to include financial or legal advice or proposed medical treatments should be treated with due caution. Vixra.org will not be responsible for any consequences of actions that result from any form of use of any documents on this website.
Add your own feedback and questions here:
You are equally welcome to be positive or negative about any paper but please be polite. If you are being critical you must mention at least one specific error, otherwise your comment will be deleted as unhelpful.