Wu Lei, Hui Hui, Wang Li-Juan, Wang Hao, Liu Qiu-Fang, Han Su-Xia
Department of Radiotherapy, The First Affiliated Hospital of Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Center of Gynecological Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710068, P.R. China.
Oncol Rep. 2015 May;33(5):2309-18. doi: 10.3892/or.2015.3840. Epub 2015 Mar 6.
Accumulating evidence has demonstrated that microRNAs (miRNAs) are involved in multiple processes in cancer development and progression. miR-326 has been identified as a tumor suppressor miRNA in several types of human cancer. However, the specific function of miR-326 and its target the nin one binding protein (NOB1) in colorectal carcinoma (CRC) remains unclear. In the present study, we found that miR-326 inhibited cell proliferation, migration and invasion, and induced cell apoptosis and cell cycle arrest of CRC cells by directly targeting NOB1. Furthermore, the upregulation of miR-326 in CRC cells was revealed to be associated with a feedback loop involving downregulation of the NOB1, which mimics the phenotype induced by miR-326. Importantly, we found that the CRC patients with high expression of miR-326 or low expression of NOB1 tend to obtain a better prognosis. Thus, for the first time, we provide convincing evidence that downregulation of miR-326 inhibited tumor proliferation and tumor metastasis by directly targeting NOB1 in CRC. NOB1 and miR-326 could be potential therapeutic targets for CRC.
越来越多的证据表明，微小RNA（miRNA）参与了癌症发生和发展的多个过程。miR-326已被确定为几种人类癌症中的一种肿瘤抑制性miRNA。然而，miR-326及其靶点核仁素结合蛋白1（NOB1）在结直肠癌（CRC）中的具体功能仍不清楚。在本研究中，我们发现miR-326通过直接靶向NOB1抑制CRC细胞的增殖、迁移和侵袭，并诱导细胞凋亡和细胞周期停滞。此外，CRC细胞中miR-326的上调与一个涉及NOB1下调的反馈环有关，该反馈环模拟了miR-326诱导的表型。重要的是，我们发现miR-326高表达或NOB1低表达的CRC患者往往预后较好。因此，我们首次提供了令人信服的证据，即miR-326的下调通过直接靶向CRC中的NOB1抑制肿瘤增殖和肿瘤转移。NOB1和miR-326可能是CRC的潜在治疗靶点。
