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Background <p>Cervical cancer (CVC), a common gynecological malignant tumor, ranks second among female malignant tumors worldwide. However, the effects of miR-33a-5p, fat mass and obesity-associated protein (FTO), and phosphodiesterase 4B (PDE4B) on CVC are still unclear. Therefore, this study aims to explore the mechanisms of miR-33a-5p, FTO, and PDE4B on CVC cells, and first verify their expression patterns in clinical CVC tissues. The CCK-8 and Transwell assays were used to determine the cell viability and invasion of SiHa and C-33 A cells, respectively. The starBase-Pan Cancer analysis based on the TCGA database was employed to predict the expression level of PDE4B in CVC patients. The qRT-PCR and Western blot approaches were adopted to determine the gene and protein expression levels of miR-33a-5p, FTO, and PDE4B of clinical tissues and CVC cells, respectively. The Targetscan 7.2 and miRwalk databases, as well as the dual-luciferase report, were applied to predict and verify the targeted relationship between miR-33a-5p and FTO, respectively. The RM2Target database and methylated RNA immunoprecipitation-qPCR were used to predict the target gene of FTO-mediated m<sup>6</sup>A demethylation and verify the effects of FTO on PDE4B m<sup>6</sup>A demethylation level, respectively. An actinomycin D-mediated mRNA stability assay was conducted to clarify the regulatory effect of FTO on PDE4B mRNA stability. MiR-33a-5p and PDE4B were lowly expressed, and FTO was highly expressed in clinical CVC tissues and cell lines. Overexpressing miR-33a-5p reduced the cell viability, invasion, and FTO expression of SiHa and C-33 A cells. Overexpressing FTO reversed the effects of overexpressed miR-33a-5p on cell viability and invasion without altering miR-33a-5p expression in SiHa and C-33 A cells. MiR-33a-5p targeted and inhibited FTO in SiHa and C-33 A cells. Knocking down FTO decreased cell viability and invasion, and increased PDE4B expression in SiHa and C-33 A cells. Inhibiting PDE4B reversed the effects of down-regulated FTO on cell viability and invasion without altering FTO expression in SiHa and C-33 A cells. FTO downregulated PDE4B by mediating m<sup>6</sup>A demethylation in SiHa and C-33 A cells, and overexpressing FTO significantly reduced the mRNA stability of PDE4B in SiHa and C-33 A cells. Taken together, microRNA-33a-5p alleviates CVC by regulating PDE4B via FTO-mediated m<sup>6</sup>A demethylation and subsequent reduction of PDE4B mRNA stability, which constitutes a novel regulatory axis in cervical cancer progression.</p>

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MicroRNA-33a-5p alleviates cervical cancer by regulating PDE4B through FTO-mediated m6A demethylation

  • 期刊论文

  • 发表日期：

    2026年5月11日

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  • Bo Sun,
  • Xiaoyan Huang,
  • Jiqin Xu,
  • Fujun Li,
  • Hongguo Dong

摘要

Background

Cervical cancer (CVC), a common gynecological malignant tumor, ranks second among female malignant tumors worldwide. However, the effects of miR-33a-5p, fat mass and obesity-associated protein (FTO), and phosphodiesterase 4B (PDE4B) on CVC are still unclear. Therefore, this study aims to explore the mechanisms of miR-33a-5p, FTO, and PDE4B on CVC cells, and first verify their expression patterns in clinical CVC tissues. The CCK-8 and Transwell assays were used to determine the cell viability and invasion of SiHa and C-33 A cells, respectively. The starBase-Pan Cancer analysis based on the TCGA database was employed to predict the expression level of PDE4B in CVC patients. The qRT-PCR and Western blot approaches were adopted to determine the gene and protein expression levels of miR-33a-5p, FTO, and PDE4B of clinical tissues and CVC cells, respectively. The Targetscan 7.2 and miRwalk databases, as well as the dual-luciferase report, were applied to predict and verify the targeted relationship between miR-33a-5p and FTO, respectively. The RM2Target database and methylated RNA immunoprecipitation-qPCR were used to predict the target gene of FTO-mediated m6A demethylation and verify the effects of FTO on PDE4B m6A demethylation level, respectively. An actinomycin D-mediated mRNA stability assay was conducted to clarify the regulatory effect of FTO on PDE4B mRNA stability. MiR-33a-5p and PDE4B were lowly expressed, and FTO was highly expressed in clinical CVC tissues and cell lines. Overexpressing miR-33a-5p reduced the cell viability, invasion, and FTO expression of SiHa and C-33 A cells. Overexpressing FTO reversed the effects of overexpressed miR-33a-5p on cell viability and invasion without altering miR-33a-5p expression in SiHa and C-33 A cells. MiR-33a-5p targeted and inhibited FTO in SiHa and C-33 A cells. Knocking down FTO decreased cell viability and invasion, and increased PDE4B expression in SiHa and C-33 A cells. Inhibiting PDE4B reversed the effects of down-regulated FTO on cell viability and invasion without altering FTO expression in SiHa and C-33 A cells. FTO downregulated PDE4B by mediating m6A demethylation in SiHa and C-33 A cells, and overexpressing FTO significantly reduced the mRNA stability of PDE4B in SiHa and C-33 A cells. Taken together, microRNA-33a-5p alleviates CVC by regulating PDE4B via FTO-mediated m6A demethylation and subsequent reduction of PDE4B mRNA stability, which constitutes a novel regulatory axis in cervical cancer progression.