Impact of ALKBH5 demethylase on the progression of thyroid cancer cells via m6A modification of CKMT2-AS1

Thyroid cancer (TC) has the highest incidence rate among head and neck malignancies. m6A regulators are aberrantly expressed and closely associated with the development of a variety of diseases and cancers. However, the role of m6A regulators in the development of TC is unclear. The m6A levels and expression of m6A regulatory molecules in cancer tissues and paracancerous tissues were assessed using qRT-PCR and Western blot analysis, respectively. Subsequently, the impact of ALKBH5 on papillary TC cell proliferation and apoptosis was investigated through EDU staining, clone formation assay, and flow cytometry. The m6A levels of ALKBH5 target genes were determined by m6A MeRIP–qRT-PCR. RIP was employed to confirm the interaction between the target gene and “reader” proteins. The level of m6A exhibited a significant increase, while the level of ALKBH5 demonstrated a significant decrease in TC tissues. The knockdown of ALKBH5 resulted in a substantial increase in proliferation and a decrease in apoptosis of TC cells. After ALKBH5 knockdown, there was an elevation in both m6A levels and stability of CKMT2-AS1 within TC cells. YTHDC1 knockdown led to decreased stability of CKMT2-AS1 within TC cells. Knockdown of YTHDC1 reversed the ability of ALKBH5 knockdown to promote proliferation and inhibit apoptosis in TC cells. The role of ALKBH5 in TC cells is to suppress their malignant biological behavior, and this effect may be mediated through the signaling pathway involving ALKBH5/CKMT2-AS1/YTHDC1. This discovery has the potential to identify new therapeutic targets for treating TC.