Tet methylcytosine dioxygenase 2 suppresses renal cell cancer proliferation and metastasis by regulating the miR-200c-SCD axis

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Abstract
Tet methylcytosine dioxygenase 2 (TET2) acts as an antioncogene that is investigated in different cancers. But the effects of TET2 in renal cell cancer (RCC) is still known little. Here, quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence were performed to exam gene and protein expression. Cell proliferation was measured using Cell Counting Kit-8 (CCK-8). Transwell assay was performed to detect cell metastasis viability. Flow cytometry was performed to analyze the cell cycle and cell apoptosis. The effects of TET2 on RCC growth in vivo was analyzed using a mouse xenograft model.We found that TET2 and miR-200c were decreased in RCC tissues, and hypermethylation of miR-200c promoter was found. Overexpression of TET2 promoted miR-200c expression by reducing miR-200c promoter methylation. Additionally, overexpression of TET2 or miR-200c suppressed cell growth and metastasis. Also, knockdown of miR-200c could moderate TET2 mediated cell growth inhibition. Furthermore, we found miR-200c directly regulates Stearoyl-CoA desaturase (SCD) gene expression. Moreover, in vivo experiment results confirmed that TET2 inhibited tumor growth. In conclusion, TET2 acts as an antioncogene in RCC by regulating the miR-200c-SCD axis and providing a potential target for RCC diagnosis and treatment.

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