MiR-138 is a potent regulator of the heterogenous MYC transcript population in cancers.

Autor: Desi N; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore., Teh V; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Tong QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Lim CY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Tabatabaeian H; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Chew XH; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Sanchez-Mejias A; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore.; Department of Experimental and Health Sciences, Pompeu Fabra University, 08003, Barcelona, Spain., Chan JJ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Zhang B; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Pitcheshwar P; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore., Siew BE; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore., Wang S; Department of Pathology, National University Health System, Singapore, Singapore., Lee KC; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Chong CS; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Cheong WK; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Lieske B; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Tan IJ; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Tan KK; Department of Surgery, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Division of Colorectal Surgery, University Surgical Cluster, National University Health System, Singapore, Singapore., Tay Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore, 117599, Singapore. yvonnetay@nus.edu.sg.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore. yvonnetay@nus.edu.sg.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2022 Feb; Vol. 41 (8), pp. 1178-1189. Date of Electronic Publication: 2021 Dec 22.
DOI: 10.1038/s41388-021-02084-x
Abstrakt: 3'UTR shortening in cancer has been shown to activate oncogenes, partly through the loss of microRNA-mediated repression. This suggests that many reported microRNA-oncogene target interactions may not be present in cancer cells. One of the most well-studied oncogenes is the transcription factor MYC, which is overexpressed in more than half of all cancers. MYC overexpression is not always accompanied by underlying genetic aberrations. In this study, we demonstrate that the MYC 3'UTR is shortened in colorectal cancer (CRC). Using unbiased computational and experimental approaches, we identify and validate microRNAs that target the MYC coding region. In particular, we show that miR-138 inhibits MYC expression and suppresses tumor growth of CRC and hepatocellular carcinoma (HCC) cell lines. Critically, the intravenous administration of miR-138 significantly impedes MYC-driven tumor growth in vivo. Taken together, our results highlight the previously uncharacterized shortening of the MYC 3'UTR in cancer, and identify miR-138 as a potent regulator of the heterogenous MYC transcript population.
(© 2021. The Author(s).)
Databáze: MEDLINE
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