Li Haoming, Wang Gang, Yu Yipeng, Jian Wengang, Zhang Daming, Wang Yongquan, Wang Tengda, Meng Yuyang, Yuan Chao, Zhang Cheng
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.
J Cancer. 2018 Nov 24;9(24):4618-4626. doi: 10.7150/jca.27673. eCollection 2018.
: This study investigated the biological function of the gene MAN1C1 α-mannosidase in renal cell carcinoma. It has been reported that MAN1C1 is probably a potential tumor suppressor gene in Wilms. However, the role of MAN1C1 in human clear cell renal cell carcinoma (ccRCC) has not been reported. : In this study, MAN1C1 gene over-expression was used to transfect human renal cancer cell lines 786-O and OS-RC-2 to study apoptosis and the underlying mechanisms which influence epithelial-mesenchymal transition. : MAN1C1 was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. We revealed that over-expression MAN1C1 showed anti-tumor effect by inducing apoptosis, as determined by Cell Counting Kit-8 (CCK-8) assay, cell cycle analysis, and western blot analysis. What's more, MAN1C1 over-expression remarkably increased the ratio of Bax/Bcl-2 and inhibited epithelial-mesenchymal transition by increasing the expression of E-CA. In addition, the ratio of Bax/Bcl-2 and E-CA were also increased in MAN1C1 gene over-expression renal cancer cells compared with the control cells. : We find that re-expression of silenced MAN1C1 in ccRCC cell lines inhibited cell viability, colony formation, induced apoptosis, suppressed cell invasion and migration. In conclusion, MAN1C1 is a novel functional tumor suppressor in renal carcinogenesis. This is the first time that the function of MAN1C1 gene has been verified in the renal tumor tissue so far.
本研究调查了基因MAN1C1α-甘露糖苷酶在肾细胞癌中的生物学功能。据报道，MAN1C1可能是肾母细胞瘤中的一种潜在肿瘤抑制基因。然而，MAN1C1在人类透明细胞肾细胞癌（ccRCC）中的作用尚未见报道。：在本研究中，采用MAN1C1基因过表达转染人肾癌细胞系786-O和OS-RC-2，以研究细胞凋亡及影响上皮-间质转化的潜在机制。：MAN1C1在ccRCC中表达下调，且与ccRCC的临床病理因素及预后相关。我们发现，通过细胞计数试剂盒-8（CCK-8）检测、细胞周期分析和蛋白质印迹分析确定，MAN1C1过表达通过诱导细胞凋亡显示出抗肿瘤作用。此外，MAN1C1过表达显著增加了Bax/Bcl-2的比值，并通过增加E-CA的表达抑制上皮-间质转化。此外，与对照细胞相比，MAN1C1基因过表达的肾癌细胞中Bax/Bcl-2的比值和E-CA也增加。：我们发现，在ccRCC细胞系中重新表达沉默的MAN1C1可抑制细胞活力、集落形成，诱导细胞凋亡，抑制细胞侵袭和迁移。总之，MAN1C1是肾致癌过程中一种新的功能性肿瘤抑制因子。这是迄今为止首次在肾肿瘤组织中验证MAN1C1基因的功能。
