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miR-148a 是一种雄激素反应性 microRNA,通过抑制其靶标 CAND1 的表达来促进 LNCaP 前列腺细胞的生长。

miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression.

机构信息

Department of Anti-Aging Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.

出版信息

Prostate Cancer Prostatic Dis. 2010 Dec;13(4):356-61. doi: 10.1038/pcan.2010.32. Epub 2010 Sep 7.

Abstract

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.

摘要

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。

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