School of Life Science, Guangdong Pharmaceutical University, Guangzhou, China.
PLoS One. 2013 Aug 5;8(8):e70300. doi: 10.1371/journal.pone.0070300. Print 2013.
Emerging evidence indicate that microRNAs (miRNAs) may play important roles in cancer. Aberrant expression of miRNAs has been frequently identified in different human malignancies, including colorectal cancer (CRC). However, the mechanism by which deregulated miRNAs impact the development of CRC remains largely elusive. In this study, we show that miR-124 is significantly down-regulated in CRC compared to adjacent non-tumor colorectal tissues. MiR-124 suppresses the expression of STAT3 by directly binding to its 3'-untranslated region (3'-UTR). Overexpression of miR-124 led to increased apoptosis of CRC cells and reduced tumor growth in vitro and in vivo. Knocking down STAT3 expression by specific siRNA suppressed the growth of CRC cells in vitro and in vivo, resembling that of miR-124 overexpression. Moreover, overexpression of STAT3 in miR-124-transfected CRC cells effectively rescued the inhibition of cell proliferation caused by miR-124. These data suggest that miR-124 serves as a tumor suppressor by targeting STAT3, and call for the use of miR-124 as a potential therapeutic tool for CRC, where STAT3 is often hyper-activated.
新出现的证据表明,microRNAs(miRNAs)可能在癌症中发挥重要作用。miRNAs 的异常表达已在不同的人类恶性肿瘤中频繁被发现,包括结直肠癌(CRC)。然而,失调的 miRNAs 如何影响 CRC 的发展在很大程度上仍未被揭示。在这项研究中,我们发现与相邻的非肿瘤结直肠组织相比,miR-124 在 CRC 中显著下调。miR-124 通过直接结合其 3'非翻译区(3'UTR)来抑制 STAT3 的表达。miR-124 的过表达导致 CRC 细胞凋亡增加,体外和体内肿瘤生长减少。特异性 siRNA 敲低 STAT3 表达可抑制 CRC 细胞的体外和体内生长,类似于 miR-124 的过表达。此外,在 miR-124 转染的 CRC 细胞中过表达 STAT3 可有效挽救 miR-124 引起的细胞增殖抑制。这些数据表明,miR-124 通过靶向 STAT3 作为肿瘤抑制因子发挥作用,并呼吁将 miR-124 用作 CRC 的潜在治疗工具,其中 STAT3 通常过度激活。