AlkB Homolog 5 Regulates Hexokinase 2-Mediated Glycolysis and Participates in the Progression of Endometriosis

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AlkB homolog 5 upregulates hexokinase 2 to promote glycolysis, invasion, and migration, thereby contributing to endometriosis progression, and its inhibition slows disease progression in a mouse model.

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Abstract

Endometriosis is a common gynecological endocrine disease with unclear pathogenesis. Evidence suggests enhanced aerobic glycolysis in ectopic endometrium of endometriosis. The role of N6-methyladenosine (m6A) modification in female reproductive diseases has been revealed in recent years, and it is involved in the regulation of glycolysis in a variety of diseases. Here, we investigated the regulatory effect of m6A modification on glycolysis and its role in endometriosis. RNA sequencing of ectopic endometrium of endometriosis and normal endometrium revealed that hexokinase 2 (HK2) a glycolysis-related gene, was significantly up-regulated in ectopic endometrium of endometriosis. Meanwhile, this result was supported by immunohistochemistry. Subsequently, we found that AlkB homolog 5 (ALKBH5) could upregulate HK2 in human endometrial stromal cells (THESCs). Up-regulation of ALKBH5 promoted glycolysis, invasion, and migration of THESCs, which could be alleviated by 2-Deoxy-d-glucose (2-DG). Furthermore, knockdown of HK2 in THESCs overexpressing ALKBH5 significantly attenuated the promoting effects of ALKBH5 on glycolysis, migration, and invasion of THESCs. Moreover, an ALKBH5 inhibitor, 5-Carboxy-8-hydroxyquinoline (IOX1) was found to inhibit the progression of endometriosis and glycolysis in a mouse model of endometriosis. In conclusion, ALKBH5 promoted glycolysis by up-regulating HK2 and contributed to the progression of endometriosis. ALKBH5 may be a new target for the treatment of endometriosis.

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Outcome instruments

Enzian

Condition tags

endometriosis

MeSH descriptors

AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase AlkB Homolog 5, RNA Demethylase

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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