MicroRNA-493-5p-mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion

Ken Yasukawa, Lee Chuen Liew, Keitaro Hagiwara, Ai Hironaka-Mitsuhashi, Xian Yang Qin, Yutaka Furutani, Yasuhito Tanaka, Hitoshi Nakagama, Soichi Kojima, Takashi Kato, Takahiro Ochiya, Luc Gailhouste

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Primary hepatic tumors mainly include hepatocellular carcinoma (HCC), which is one of the most frequent causes of cancer-related deaths worldwide. Thus far, HCC prognosis has remained extremely poor given the lack of effective treatments. Numerous studies have described the roles played by microRNAs (miRNAs) in cancer progression and the potential of these small noncoding RNAs for diagnostic or therapeutic applications. The current consensus supports the idea that direct repression of a wide range of oncogenes by a single key miRNA could critically affect the malignant properties of cancer cells in a synergistic manner. In this study, we aimed to investigate the oncogenes controlled by miR-493-5p, a major tumor suppressor miRNA that inactivates miR-483-3p oncomir in hepatic cancer cells. Using global gene expression analysis, we highlighted a set of candidate genes potentially regulated by miR-493-5p. In particular, the canonical MYCN protooncogene (MYCN) appeared to be an attractive target of miR-493-5p given its significant inhibition through 3′-UTR targeting in miR-493-5p-rescued HCC cells. We showed that MYCN was overexpressed in liver cancer cell lines and clinical samples from HCC patients. Notably, MYCN expression levels were inversely correlated with miR-493-5p in tumor tissues. We confirmed that MYCN knockdown mimicked the anticancer effect of miR-493-5p by inhibiting HCC cell growth and invasion, whereas MYCN rescue hindered miR-493-5p activity. In summary, miR-493-5p is a pivotal miRNA that modulates various oncogenes after its reexpression in liver cancer cells, suggesting that tumor suppressor miRNAs with a large spectrum of action could provide valuable tools for miRNA replacement therapies.

Original languageEnglish
Pages (from-to)869-880
Number of pages12
JournalCancer Science
Volume111
Issue number3
DOIs
Publication statusPublished - 2020 Mar 1

Keywords

  • cancer therapy
  • hepatocellular carcinoma
  • microRNA
  • oncogene
  • tumor suppressor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'MicroRNA-493-5p-mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion'. Together they form a unique fingerprint.

  • Cite this

    Yasukawa, K., Liew, L. C., Hagiwara, K., Hironaka-Mitsuhashi, A., Qin, X. Y., Furutani, Y., Tanaka, Y., Nakagama, H., Kojima, S., Kato, T., Ochiya, T., & Gailhouste, L. (2020). MicroRNA-493-5p-mediated repression of the MYCN oncogene inhibits hepatic cancer cell growth and invasion. Cancer Science, 111(3), 869-880. https://doi.org/10.1111/cas.14292