Department of Anti-Aging Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Prostate Cancer Prostatic Dis. 2010 Dec;13(4):356-61. doi: 10.1038/pcan.2010.32. Epub 2010 Sep 7.
Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR-148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3'-untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.
近年来癌症生物学的进展表明，microRNAs（miRNAs）参与了癌症相关基因的调控，它们可以作为肿瘤抑制因子或癌基因发挥作用。在前列腺癌中，有证据表明雄激素依赖性基因网络对肿瘤生长有贡献，尽管 miRNA 在前列腺癌中的确切功能仍有待研究。在这里，我们通过对 LNCaP 前列腺癌细胞的短 RNA 测序分析鉴定了雄激素反应性 miRNAs。在已知序列的 10 个 miRNAs 中，我们确定 miR-148a 通过与 CAND1 mRNA 的 3'-UTR 结合，降低了 cullin 相关和 neddylation 相关 1（CAND1）的表达，CAND1 是 SKP1-Cullin1-F-box（SCF）泛素连接酶的负调节剂。通过小干扰 RNA 敲低 CAND1 促进了 LNCaP 细胞的增殖。我们的研究表明 miR-148a 可能对人类前列腺癌的生长有贡献。
