FTO-stabilized lncRNA HOXC13-AS epigenetically upregulated FZD6 and activated Wnt/β-catenin signaling to drive cervical cancer proliferation, invasion, and EMT.

Tongfei Wang, Weina Li, Biaofei Ye, Shuangyan Zhang, Xin Lei, Da Zhang

Journal of B.U.ON. : official journal of the Balkan Union of Oncology 2021 Jul-Aug

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Cervical cancer (CC) is the third most prevalent malignancy in women. Frizzled class receptor 6 (FZD6) is demonstrated to either activate or repress the activity of Wnt/β-catenin pathway, a crucial signaling involved in cancer development. However, the role of FZD6 in CC is unknown. The present study explored the function of FZD6 and its mechanism in CC. The levels of FZD6, HOXC13-AS were detected in CC specimens and CC cell lines via qRT-PCR. Cell proliferation and invasion was explored via CCK-8 assay, colony formation assay and transwell assay. Luciferase reporter analysis, FISH, subcellular fractionation, chromatin immunoprecipitation and RNA immunoprecipitation were performed for investigating the molecular mechanism. FZD6 was up-regulated in CC. FZD6 silence retarded proliferation, invasion, and epithelial-to-mesenchymal transition (EMT), and inactivated Wnt/β-catenin. HOXC13 antisense RNA (HOXC13-AS) was up-regulated in CC and positively correlated with FZD6. Mechanistically, HOCX13-AS1 augmented FZD through cAMP-response element binding protein-binding protein (CBP)-modulated histone H3 on lysine 27 acetylation (H3K27ac). Additionally, fat mass and obesity-associated protein (FTO) reduced N6-methyladenosine (m6A) and stabilized HOXC13-AS in CC. In conclusion, this study firstly showed that FTO-stabilized HOXC13-AS epigenetically up-regulated FZD6 and activated Wnt/β-catenin signaling to drive CC proliferation, invasion, and EMT, suggesting HOXC13-AS as a potential target for CC treatment.

Citation

Tongfei Wang, Weina Li, Biaofei Ye, Shuangyan Zhang, Xin Lei, Da Zhang. FTO-stabilized lncRNA HOXC13-AS epigenetically upregulated FZD6 and activated Wnt/β-catenin signaling to drive cervical cancer proliferation, invasion, and EMT. Journal of B.U.ON. : official journal of the Balkan Union of Oncology. 2021 Jul-Aug;26(4):1279-1291