Open AccessThe HOXC‐AS2/miR‐876‐5p/HKDC1 axis regulates endometrial cancer progression in a high glucose‐related tumor microenvironment
Author(s) -
Guo Jing,
Ye Feng,
Xie Wenli,
Zhang Xinxin,
Zeng Ru,
Sheng Wang,
Mi Yanjun,
Sheng Xiugui
Publication year - 2022
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.15384
Subject(s) - pyroptosis , tumor microenvironment , proinflammatory cytokine , cancer research , transcriptome , biology , microbiology and biotechnology , inflammation , programmed cell death , apoptosis , chemistry , immunology , biochemistry , gene expression , tumor cells , gene
The tumor microenvironment (TME) is related to chronic inflammation and is currently identified as a risk factor for the occurrence and development of endometrial cancer (EC). Pyroptosis is a new proinflammatory form of programmed cell death that plays a critical role in the progression of multiple diseases. However, the important role of pyroptosis in high‐glucose (HG)‐related EC and the underlying molecular mechanisms remain elusive. In the present study, transcriptome high‐throughput sequencing revealed significantly higher hexokinase domain‐containing 1 (HKDC1) expression in EC patients with diabetes than in EC patients with normal glucose. Mechanistically, HKDC1 regulates HG‐induced cell pyroptosis by modulating the production of reactive oxygen species and pyroptosis‐induced cytokine release in EC. In addition, HKDC1 regulates TME formation by enhancing glycolysis, promoting a metabolic advantage in lactate‐rich environments to further accelerate EC progression. Subsequently, miR‐876‐5p was predicted to target the HKDC1 mRNA, and HOXC‐AS2 was identified to potentially inhibit the miR‐876‐5p/HKDC1 axis in regulating cell pyroptosis in HG‐related EC. Collectively, we elucidated the regulatory role of the HOXC‐AS2/miR‐876‐5p/HKDC1 signal transduction axis in EC cell pyroptosis at the molecular level, which may provide an effective therapeutic target for patients with diabetes who are diagnosed with EC.