Elevated MicroRNA-31 Expression Regulates Colorectal Cancer Progression by Repressing Its Target Gene SATB2
Elevated MicroRNA-31 Expression Regulates Colorectal Cancer Progression by Repressing Its Target Gene SATB2
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MicroRNA-31 表达升高通过抑制其靶基因 SATB2 来调节结直肠癌进展
DOI：
10.1371/journal.pone.0085353
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发表时间：
2013-12-30
期刊：
影响因子：
3.7
通讯作者：
Ding, Yan-Qing
中科院分区：
文献类型：
--
作者：
Yang, Min-Hui;Yu, Jiang;Ding, Yan-Qing
一些研究已经提出了越来越多的证据支持这一假说，即miRNAs在肿瘤发生的多个过程中发挥关键作用，包括细胞生长、凋亡、分化和转移。在本研究中，我们研究了miR-31在结直肠癌(CRC)侵袭性中的潜在作用及其潜在机制。我们发现，来自转移灶的结直肠癌细胞和有淋巴结转移的人原发结直肠癌组织中miR-31的表达增加。此外，miR-31的高水平表达与结直肠癌患者更具侵袭性和预后不良的表型显著相关(p<；0.05)。在结直肠癌细胞中稳定过表达miR-31足以促进细胞在体外的增殖、侵袭和迁移。它也促进了肿瘤在体内的生长和转移。进一步的研究表明，miR-31可以直接与SATB2基因的3‘非翻译区(3’UTR)结合，进而抑制SATB2的mRNA和蛋白表达。瞬时转染编码SATB2全序列的pCAG-SATB2载体异位表达SATB2可以逆转miR-31对结直肠癌发生发展的影响。此外，结直肠癌细胞异位过表达miR-31可诱导上皮间充质转化(EMT)。我们的结果表明miR-31的上调通过直接抑制SATB2在体外和体内对结直肠癌细胞的增殖、侵袭和转移起重要作用，提示miR-31在结直肠癌的预后预测和治疗中具有潜在的应用价值。
Several studies have brought about increasing evidence to support the hypothesis that miRNAs play a pivotal role in multiple processes of carcinogenesis, including cell growth, apoptosis, differentiation, and metastasis. In this study, we investigated the potential role of miR-31 in colorectal cancer (CRC) aggressiveness and its underlying mechanisms. We found that miR-31 increased in CRC cells originated from metastatic foci and human primary CRC tissues with lymph node metastases. Furthermore, the high-level expression of miR-31 was significantly associated with a more aggressive and poor prognostic phenotype of patients with CRC (p < 0.05). The stable over-expression of miR-31 in CRC cells was sufficient to promote cell proliferation, invasion, and migration in vitro. It facilitated tumor growth and metastasis in vivo too. Further studies showed that miR-31 can directly bind to the 3’untranslated region (3’UTR) of SATB2 mRNA and subsequently repress both the mRNA and protein expressions of SATB2. Ectopic expression of SATB2 by transiently transfected with pCAG-SATB2 vector encoding the entire SATB2 coding sequence could reverse the effects of miR-31 on CRC tumorigenesis and progression. In addition, ectopic over-expression of miR-31 in CRC cells induced epithelial-mesenchymal transition (EMT). Our results illustrated that the up-regulation of miR-31 played an important role in CRC cell proliferation, invasion, and metastasis in vitro and in vivo through direct repressing SATB2, suggesting a potential application of miR-31 in prognosis prediction and therapeutic application in CRC.