Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/β-catenin signaling
- J Nutr Biochem. 2024 Feb:124:109489. doi: 10.1016/j.jnutbio.2023.109489.
- 1. Departments of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
- 2. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China; National Clinical Research Center for Obstetrics and Gynecology (Peaking University Third Hospital), Beijing, China; Key Laboratory of Assisted Reproduction (Peaking University), Ministry of Education, Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
- 3. School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, Shanxi, China.
- 4. Departments of Obstetrics and Gynecology, Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address: [email protected].
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.