J Cancer 2018; 9(24):4618-4626. doi:10.7150/jca.27673

Research Paper

α-1,2-Mannosidase MAN1C1 Inhibits Proliferation and Invasion of Clear Cell Renal Cell Carcinoma

Haoming Li1, Gang Wang1, Yipeng Yu1, Wengang Jian1, Daming Zhang2, Yongquan Wang1, Tengda Wang1, Yuyang Meng1, Chao Yuan1, Cheng Zhang1✉

1. Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
2. Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

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Citation:
Li H, Wang G, Yu Y, Jian W, Zhang D, Wang Y, Wang T, Meng Y, Yuan C, Zhang C. α-1,2-Mannosidase MAN1C1 Inhibits Proliferation and Invasion of Clear Cell Renal Cell Carcinoma. J Cancer 2018; 9(24):4618-4626. doi:10.7150/jca.27673. Available from http://www.jcancer.org/v09p4618.htm

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: tumor growth, MAN1C1, Bax/Bcl-2, gene over-expression