Abstract 4948: Overexpressions of miR-34 family suppress the invasive growth of malignant melanoma with wild type p53 genes

Abstract Malignant melanoma is a highly aggressive neoplasm with severe metastatic potential. In recent decades, the incidence of malignant melanoma has steadily increased. Particularly worrying features of this tumor are its increasing incidence and its capacity for rapid metastatic spread. MicroRNAs represent a class of endogenously expressed, small non-coding RNAs that regulate gene expression. As a consequence of disease, the translation of these mRNAs is inhibited or destabilized resulting in downregulation of the encoded protein. A few microRNAs have been classified as oncogenes or tumor suppressor genes as their expression is altered in tumors, and in some cases, this has been shown to contribute to the phenotypes of cancer cells. Recently, microRNA-34 (miR-34) was identified as a mediator of tumor suppression by p53. The miR-34 family comprises three processed microRNAs (miR-34a/b/c) that are encoded by two different genes: miR-34a is encoded by its own transcript, whereas miR-34b and miR-34c share a common primary transcript. Many reports have suggested that miR-34s contribute to inhibition of invasion or metastasis in various tumors. These reports suggest that miR-34s play important roles as inhibitors of tumor growth. However, the biological characteristics of miR-34s in human malignant melanoma are not well understood. In this study, we performed real-time reverse transcription PCR to evaluate expressions of the miR-34 family in four human melanoma cell lines that contained the wild type p53 gene (A375, G361, SK-MEL-24, and C32TG). We also examined the generative and invasive characteristics of these cell lines using the cell proliferation assay and invasion/migration assay. 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; SK-MEL-24, 0.3621, 2.5659, 8.5907; C32TG, 2.1630, 2.1091, 8.4425. The cell doubling times of these cell lines were as follows; A375 23:23, G361 68:24, SK-MEL-24 67:03, and C32TG 47:22. In vitro generation times of G361 and SK-MEL-24, which showed increased expressions of miR-34c, were significantly longer than that of A375 with decreased expression of miR-34c (p=0.0063, ANOVA). %Invasions of four cell lines were as follows; A375 44.0%, G361 22.4%, SK-MEL-24 45.0%, and C32TG 13.8%. In vitro invasiveness of G361 and C32TG, which showed increased expressions of miR-34a were significantly suppressed (p=0.005, ANOVA). These findings suggest that overexpressions of miR-34a and c suppress invasive and generative potentials respectively in human malignant melanoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4948. doi:10.1158/1538-7445.AM2011-4948