FTO promotes the cervical cancer progression via regulation of FGF2 expression.

BACKGROUND: Cervical cancer remains one of the most common gynecological malignancies worldwide, with epigenetic RNA modifications playing a critical role in its development. This study aims to investigate the role of fat mass and obesity-associated protein (FTO) in cervical cancer progression and its impact on N6-methyladenosine (m6A) RNA methylation, focusing on Fibroblast Growth Factor 2 (FGF2) as a key downstream mediator. METHODS: We analyzed FTO expression in adjacent normal and cervical cancer tissues by using immunohistochemistry (IHC), Western blot, and q-PCR. We also examined FTO expression and m6A modification levels in cervical cancer cell lines versus control cell lines. To investigate the impact of FTO overexpression and knockdown on cell proliferation and apoptosis, a series of functional assays, including CCK-8, flow cytometry, and immunofluorescence staining, were carried out. Furthermore, we investigated the regulation of FGF2 by FTO using the GEPIA database, qRT-PCR, and Western blot. RESULTS: There was a notable elevation of FTO expression in cervical cancer tissues as opposed to the adjacent normal tissues. Increased levels of FTO protein and mRNA were detected in tumor tissues, along with reduced m6A modification levels of FTO mRNA. Cervical cancer cells showed higher FTO expression and decreased m6A modification compared to control cell lines. Enhanced FTO expression in HeLa cells resulted in lower global m6A levels, increased cell proliferation, and reduced apoptosis. Conversely, FTO knockdown led to reduced cell proliferation, reduced FGF2 mRNA and protein levels, diminished lactate production, and impaired cell proliferation, and increased apoptosis. CONCLUSION: FTO significantly influences cervical cancer progression, at least in part, through m6A modification of FGF2, thereby affecting downstream signaling. Targeting FTO and its downstream effectors holds potential as a therapeutic strategy for cervical cancer treatment.