Gu Chaohui, Wang Zhiyu, Jin Zhibo, Li Guanru, Kou Yiping, Jia Zhankui, Yang Jinjian, Tian Fengyan
Department of Urology and Henan Institute of Urology, Zhengzhou Key Laboratory for Molecular Biology of Urological Tumor Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Oncotarget. 2017 Sep 8;8(54):92119-92133. doi: 10.18632/oncotarget.20786. eCollection 2017 Nov 3.
MicroRNAs have been found to be critical regulator of cancer cell biology. MicroRNA-212 (miR-212) was identified to be a critical cancer-associated microRNA playing either oncogenic functions or tumor suppressive roles in different types of human cancers. In this study, we found that the level of miR-212 in renal cell carcinoma (RCC) tissues was significantly lower than that in adjacent non-tumor tissues. Decreased level of miR-212 was associated with advanced T stage and TNM stage of RCC. The expression of miR-212 was decreased in RCC cell lines as compared with the HK-2 cell line. Overexpression of miR-212 inhibited cell viability, proliferation, migration and invasion of CAKI-2 cells. Knockdown of miR-212 increased cell viability and proliferation, migration and invasion of ACHN cells. experiments showed that miR-212 inhibited the proliferation and promoted the apoptosis of ACHN cells in nude mice and thus inhibited the tumor growth of CAKI-2 cells. Furthermore, we confirmed that X-linked inhibitor of apoptosis protein (XIAP) was the downstream target of miR-212. The expression level of miR-212 was negatively correlated with XIAP expression in RCC tissues. Moreover, XIAP mediated the tumor suppressive roles of miR-212 in RCC. Finally, we demonstrated that the aberrant expression of miR-212 and XIAP was evidently correlated with poor prognosis of RCC patients. In all, miR-212 can act as a prognostic biomarker for RCC patients and inhibits the growth and metastasis of RCC cells by inhibiting XIAP.
微小RNA已被发现是癌细胞生物学的关键调节因子。微小RNA-212（miR-212）被确定为一种与癌症相关的关键微小RNA，在不同类型的人类癌症中发挥致癌功能或肿瘤抑制作用。在本研究中，我们发现肾细胞癌（RCC）组织中miR-212的水平显著低于相邻的非肿瘤组织。miR-212水平降低与RCC的晚期T分期和TNM分期相关。与HK-2细胞系相比，RCC细胞系中miR-212的表达降低。miR-212的过表达抑制了CAKI-2细胞的活力、增殖、迁移和侵袭。敲低miR-212增加了ACHN细胞的活力、增殖、迁移和侵袭。实验表明，miR-212抑制裸鼠中ACHN细胞的增殖并促进其凋亡，从而抑制CAKI-2细胞的肿瘤生长。此外，我们证实X连锁凋亡抑制蛋白（XIAP）是miR-212的下游靶点。RCC组织中miR-212的表达水平与XIAP的表达呈负相关。此外，XIAP介导了miR-212在RCC中的肿瘤抑制作用。最后，我们证明miR-212和XIAP的异常表达与RCC患者的不良预后明显相关。总之，miR-212可作为RCC患者的预后生物标志物，并通过抑制XIAP抑制RCC细胞的生长和转移。
