Overexpression of the miR-34 family suppresses invasive growth of malignant melanoma with the wild-type p53 gene

Hitoshi Yamazaki, Tsuyoshi Chijiwa, Yoshimasa Inoue, Yoshiyuki Abe, Hiroshi Suemizu, Kenji Kawai, Masatoshi Wakui, Daisuke Furukawa, Masaya Mukai, Sadahito Kuwao, Makoto Saegusa, Masato Nakamura

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29 Citations (Scopus)

Abstract

Malignant melanoma is the most aggressive neoplasm, with severe metastatic potential. microRNAs represent a class of endogenously expressed, small non-coding RNAs that regulate gene expression. As a consequence, the translation of these mRNAs is inhibited or they are destabilized resulting in downregulation of the encoded protein. The microRNA-34 (miR-34) family, which comprises three processed microRNAs (miR-34a/b/c) was identified as the mediator of tumor suppression by p53. Many reports suggest that the miR-34s contribute to the inhibition of invasion or metastasis in various tumor types. In this study, we evaluated the expression of the miR-34 family in four human melanoma cell lines (A375, G361, C32TG and SK-MEL-24) which have the wild-type p53 gene using real-time reverse transcription PCR. We also examined their generative and invasive characteristics using the cell proliferation assay and the invasion/migration assay, respectively. All four melanoma cell lines showed significant expression of miR-34s - A375: miR-34a 0.6176, miR-34b 0.7625, miR-34c 0.7877; G361: 7.6424, 16.4127, 22.0332; C32TG: 2.1630, 2.1091, 8.4425; SK-MEL-24: 0.3621, 2.5659, 8.5907. The cell doubling times of these cell lines in h:min were as follows: A375 23:23, G361 68:24, C32TG 47:22 and SK-MEL-24 67:03. The in vitro generation times of G361 and SK-MEL-24, which showed increased expression of miR-34c, were significantly shorter than A375 with decreased expression of miR-34c (p=0.0063, ANOVA). Invasion (%) of the four cell lines was as follows: A375 44.0%, G361 22.4%, C32TG 13.8% and SK-MEL-24 45.0%. In vitro invasiveness of G361 and C32TG, which showed increased expression of miR-34a, was significantly suppressed (p=0.005, ANOVA). These results suggest that overexpression of miR-34a and c suppresses invasive and generative potentials, respectively, in human malignant melanoma.

Original languageEnglish
Pages (from-to)793-796
Number of pages4
JournalExperimental and Therapeutic Medicine
Volume3
Issue number5
DOIs
Publication statusPublished - 2012 May

Keywords

  • Melanoma
  • MicroRNA-34
  • p53

ASJC Scopus subject areas

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

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