Department of Gynecological Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
Biochem Biophys Res Commun. 2013 Nov 29;441(4):693-700. doi: 10.1016/j.bbrc.2013.10.053. Epub 2013 Oct 21.
MicroRNAs (miRNAs) are a family of small non-coding RNA molecules that regulate gene expression at post-transcriptional levels. Previous studies have shown that miR-145 is downregulated in human ovarian cancer; however, the roles of miR-145 in ovarian cancer growth and invasion have not been fully demonstrated. In the present study, Northern blot and qRT-PCR analysis indicate that miR-145 is downregulated in ovarian cancer tissues and cell lines, as well as in serum samples of ovarian cancer, compared to healthy ovarian tissues, cell lines and serum samples. Functional studies suggest that miR-145 overexpression leads to the inhibition of colony formation, cell proliferation, cell growth viability and invasion, and the induction of cell apoptosis. In accordance with the effect of miR-145 on cell growth, miR-145 suppresses tumor growth in vivo. MiR-145 is found to negatively regulate P70S6K1 and MUC1 protein levels by directly targeting their 3'UTRs. Importantly, the overexpression of p70S6K1 and MUC1 can restore the cell colony formation and invasion abilities that are reduced by miR-145, respectively. MiR-145 expression is increased after 5-aza-CdR treatment, and 5-aza-CdR treatment results in the same phenotype as the effect of miR-145 overexpression. Our study suggests that miR-145 modulates ovarian cancer growth and invasion by suppressing p70S6K1 and MUC1, functioning as a tumor suppressor. Moreover, our data imply that miR-145 has potential as a miRNA-based therapeutic target for ovarian cancer.
微小 RNA（miRNAs）是一类小的非编码 RNA 分子，可在转录后水平调节基因表达。先前的研究表明，miR-145 在人类卵巢癌中下调；然而，miR-145 在卵巢癌生长和侵袭中的作用尚未得到充分证明。在本研究中，Northern blot 和 qRT-PCR 分析表明，与健康卵巢组织、细胞系和血清样本相比，miR-145 在卵巢癌组织和细胞系以及卵巢癌患者的血清样本中下调。功能研究表明，miR-145 过表达导致集落形成、细胞增殖、细胞生长活力和侵袭的抑制，以及细胞凋亡的诱导。与 miR-145 对细胞生长的影响一致，miR-145 抑制体内肿瘤生长。发现 miR-145 通过直接靶向其 3'UTR 负调控 P70S6K1 和 MUC1 蛋白水平。重要的是，p70S6K1 和 MUC1 的过表达可以分别恢复由 miR-145 降低的细胞集落形成和侵袭能力。5-aza-CdR 处理后 miR-145 的表达增加，5-aza-CdR 处理导致与 miR-145 过表达相同的表型。我们的研究表明，miR-145 通过抑制 p70S6K1 和 MUC1 来调节卵巢癌的生长和侵袭，作为一种肿瘤抑制因子。此外，我们的数据表明 miR-145 具有作为卵巢癌基于 miRNA 的治疗靶点的潜力。
