Gong Pijun, Wang Yidong, Gao Yane, Gao Mei, Liu Lixia, Qu Ping, Jin Xinxing, Gao Qing
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
Department of Obstetrics and Gynecology, Xi'an Electric Power Central Hospital, Xi'an, Shaanxi, 710032, China.
Hum Pathol. 2017 Jul;65:53-61. doi: 10.1016/j.humpath.2016.12.026. Epub 2017 Jan 11.
Musashi1 (Msi1) is an RNA-binding protein that has been reported to be a pivotal regulator in tumorigenesis and progression in several cancers. However, its function and mechanism in cervical cancer is still unknown. In this study, Msi1 expression was found elevated in cervical cancers by immunohistochemistry and correlated with poor outcomes. Then, endogenous Msi1 was silenced in cervical cancer cell lines by short hairpin RNA, and its function and mechanism were determined. The results showed that the silencing of Msi1 in SiHa and HeLa cells inhibited the cells' migratory and invasive abilities in vitro and tumor progression in vivo. Epithelial-to-mesenchymal transition (EMT) markers were down-regulated, and Wnt activity was inhibited by the silencing of Msi1. In clinical tissues, positive correlations between Msi1 and EMT markers were found. In conclusion, Msi1, a diagnostic marker and potential therapeutic target, promoted the EMT progression through activation of the Wnt signaling pathway in cervical cancers, thereby contributing to poor prognosis.
武藏1(Msi1)是一种RNA结合蛋白,据报道在多种癌症的肿瘤发生和进展中是关键调节因子。然而,其在宫颈癌中的功能和机制仍不清楚。在本研究中,通过免疫组织化学发现Msi1在宫颈癌中表达升高,且与不良预后相关。然后,通过短发夹RNA使宫颈癌细胞系中的内源性Msi1沉默,并确定其功能和机制。结果表明,在SiHa和HeLa细胞中沉默Msi1可在体外抑制细胞的迁移和侵袭能力,并在体内抑制肿瘤进展。上皮-间质转化(EMT)标志物下调,沉默Msi1可抑制Wnt活性。在临床组织中,发现Msi1与EMT标志物之间呈正相关。总之,Msi1作为一种诊断标志物和潜在治疗靶点,通过激活Wnt信号通路促进宫颈癌中的EMT进程,从而导致预后不良。