%0 Journal Article
%T Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/β-catenin signaling.
%A Wang H
%A Wang WH
%A Wang W
%A Ma JH
%A Su XQ
%A Zhang LL
%A Hou YL
%A Liu JB
%A Ren JJ
%A Luo XL
%A Hao M
%J J Nutr Biochem
%V 124
%N 0
%D 2024 02 4
%M 37926400
%F 6.117
%R 10.1016/j.jnutbio.2023.109489
%X Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the β-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating β-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.