Carcinogenesis Advance Access originally published online on April 16, 2009
Carcinogenesis 2009 30(6):953-959; doi:10.1093/carcin/bgp094
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The miR-18a* microRNA functions as a potential tumor suppressor by targeting on K-Ras
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
* To whom correspondence should be addressed. RM177, Science Centre, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. Tel: +852 2609 6311; Fax: +852 2603 7246; Email: kwok2020{at}cuhk.edu.hk
The Ras proto-oncogene mediates a wide variety of cellular events and is frequently mutated in cancer. MicroRNAs (miRNAs) may regulate the development of cancer through their effect on the target genes. In the search of miRNAs that target on Ras, miR-18a* is the first time confirmed to target on K-Ras and furthermore not on N- and H-Ras. miR-18a* repression by transfection with anti-miR-18a* inhibitor increased the K-Ras expression as well as the luciferase activity of a reporter construct containing the 3'-untranslated region of K-Ras messenger RNA. Furthermore, the miR-18a* repression also increased the cell proliferation and promoted the anchorage-independent growth in soft agar of human squamous carcinoma A431 cells, colon adenocarcinoma HT-29 cells and fetal hepatic WRL-68 cells. On the other hand, ectopic expression of miR-18a* by transfection with miR-18a* precursor suppressed K-Ras expression, cell proliferation and anchorage-independent growth of A431 cells. The increase in cell proliferation and anchorage-independent growth upon miR-18a* repression was, however, rendered by the Ras inhibitor farnesylthiosalicylic acid. In conclusion, miR-18a* may function as a tumor suppressor by targeting on K-Ras. Therefore, the miRNA may also be a potential therapeutic agent or target for cancer therapy.
Abbreviations: FTS, farnesylthiosalicylic acid; miRNA, microRNA; mRNA, messenger RNA; MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; PCR, polymerase chain reaction; RT, reverse transcription; UTR, untranslated region
Received December 27, 2008; revised March 26, 2009; accepted April 11, 2009.
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