Vitamin D receptor suppresses proliferation and metastasis in renal cell carcinoma cell lines via regulating the expression of the epithelial Ca2+ channel TRPV5

Abstract

We previously demonstrated that transient receptor potential vanilloid subfamily 5 (TRPV5) expression was decreased in renal cell carcinoma (RCC) compared with that in normal kidney tissues, a finding that was correlated with vitamin D receptor (VDR) expression, but further investigations is warranted. The aim of this study was to elucidate whether VDR could regulate the expression of TRPV5 and affect proliferation and metastasis in RCC. In this study, we used lentivirus to conduct the model of VDR overexpression and knockdown caki-1 and 786-O RCC cell lines in vitro. The results demonstrated that VDR overexpression significantly inhibited RCC cells proliferation, migration and invasion, and promoted apoptosis by the MTT, transwell cell migration/invasion and flow cytometry assays, respectively. However, VDR knockdown in RCC cells had the opposite effect. The RNA-sequence assay, which was assessed in caki-1 cells after VDR overexpression and knockdown, also indicated that significantly differentially expressed genes were associated with cell apoptotic, differentiation, proliferation and migration. RT-PCR and western blot analysis showed that VDR knockdown increased TRPV5 expression and VDR overexpression decreased TRPV5 expression in caki-1 cells. Furthermore, knockdown of TRPV5 expression suppressed the VDR knockdown-induced change in the proliferation, migration and invasion in caki-1 cells. Taken together, these findings confirmed that VDR functions as a tumour suppressor in RCC cells and suppresses the proliferation, migration and invasion of RCC through regulating the expression of TRPV5.

MiR-125b promotes migration and invasion by targeting vitamin D receptor in renal cell carcinoma

“…VDR is one of the most studied tumor suppressor genes and acts as a transcription factor and regulates numerous physiologic processes, such as serum calcium regulation, cell proliferation and differentiation, and immunomodulatory functions 3 . We previously demonstrated that VDR overexpression signi cantly suppresses RCC cell proliferation, migration and invasion 11 . VDR could inactivate mutations, deletions, and promoter methylation to regulate cell proliferation and differentiation 4,28 .…”

“…On the other hand, VDR expression was signi cantly reduced in RCC compared to normal kidney tissue and was associated with RCC prognosis [7][8][9][10] . Speci cally, our previous studies showed that VDR overexpression could signi cantly inhibit RCC cell proliferation, migration, and invasion, and promote apoptosis and con rmed that VDR expression was associated with RCC pathological types 10,11 . These results indicate that VDR may play a key role in RCC development and progression.…”

Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy

“…It is worth mentioning that calcitriol (100 nM) also up-regulates the expression of TRPV6 in T47D breast cancer cells (Bolanz et al, 2008). Recently, Chen et al (2018) showed that the expression of the calcium channel TRPV5 inversely correlates with the expression of the VDR in renal cancer cells. Knockdown of TRPV5 in these cells inhibited cell proliferation, migration, and invasion induced by VDR knockdown.…”

Prevalência De Hepatites Virais Em Municípios Da Amazônia Legal

“…Dentre a variedade de funções e participação da VD em diferentes processos biológicos podemos citar a homeostase óssea e absorção de cálcio pelo intestino(Veldurthy et al 2016), propriedade imunomoduladora (Hardiman et al, 2016) e anti-inflamatória(Mousa et al 2018). Além disso, há evidências que a VD também regula processos de apoptose(Pan et al 2010) em células tumorais bem como a modulação da angiogênese(Bao et al 2006), proliferação, invasão e metástase tumoral(Chen et al 2018).…”