Vitamin D receptor knockdown attenuates the antiproliferative, pro-apoptotic and anti-invasive effect of vitamin D by activating the Wnt/β-catenin signaling pathway in papillary thyroid cancer

Abstract

Vitamin D and the vitamin D receptor (VDR ) complex have been reported to inhibit the growth of several types of tumor; however, their function in papillary thyroid cancer (PCT) remains unknown. In addition, the Wnt/β-catenin signaling pathway was discovered to serve a critical role in the pathology of PCT. Therefore, the present study aimed to determine the role of the VDR and its association with Wnt/β-catenin signaling in vitamin D- treated PTC cells. VDR expression was detected in human PTC cells (including MDA- T120, MDA- T85, SNU- 790 and IHH4 cells) and thyroid follicular cells (Nthy-ori 3-1 cells). SNU- 790 and IHH4 cells were infected with KD- VDR or negative control (KD-NC ) lentiviruses, treated with 1,25(OH)2D3 (the active form of vitamin D), and subsequently referred to as the KD- VDR & vitD and KD-NC & vitD groups, respectively. Additionally, PTC cells infected with KD-NC and not treated with 1,25(OH)2D3 were used as the normal control and referred to as the KD-NC group. VDR mRNA and protein expression levels were increased in MDA- T120, SNU- 790 and MDA- T85 cells compared to Nthy-ori 3-1 cells, whereas in IHH4 cells, VDR mRNA and protein expression levels were similar to Nthy-ori 3-1 cells. In SNU- 790 and IHH4 cells, cell proliferation and invasion were decreased in the KD-NC & vitD group compared with the KD-NC group, but increased in the KD- VDR & vitD group compared with the KD-NC & vitD group. Cell apoptosis was increased in the KD-NC & vitD group compared with the KD-NC group, and decreased in the KD- VDR & vitD group compared with the KD-NC & vitD group. Furthermore, the expression levels of Wnt family member 3 and catenin β1 were decreased in the KD-NC & vitD group compared with the KD-NC group, but increased in the KD- VDR & vitD group compared with the KD-NC & vitD group. In conclusion, the present study revealed that VDR- KD attenuated the antiproliferative, pro-apoptotic and anti-invasive effects of vitamin D in PTC by activating the Wnt/β-catenin signaling pathway.