Hyaluronan-mediated motility receptor-mediated aerobic glycolysis enhances stem-like properties and chemoresistance in lung adenocarcinoma

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Wenwen Yu Yubo Shi Xiaoqiong Bao Xiangxiang Chen Yangyang Ni Jincong Wang Hua Ye
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제29권 제3호, 337~347쪽, 전체 11쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2025.05.01

국문 초록

Lung adenocarcinoma (LUAD) is a global malignancy with significant chemoresistance impacting patient prognosis. The pro-tumorigenic role of hyaluronan- mediated motility receptor (HMMR) in LUAD is recognized. This study was designed to investigate the underlying mechanisms by which HMMR affects chemoresistance in LUAD. Bioinformatics presented the expression patterns of HMMR in LUAD patients and the association between HMMR levels and patient survival, followed by qRT-PCR to verify HMMR expression in LUAD tissues and cells. Further, bioinformatics was leveraged to identify the signaling pathways enriched by HMMR and its relevance to glycolytic genes, we also analyzed changes in the glycolytic activity of LUAD cells by manipulating HMMR expression. Stemness was evaluated through cell aggregation assays and Western blot, and drug responsiveness was gauged using CCK-8 assays, alongside flow cytometry for apoptosis analysis. HMMR was highly expressed in LUAD tissues and cells, and this overexpression correlated with poorer prognoses in patients. GSEA showed that HMMR was notably enriched in the glycolysis and gluconeogenesis pathways, correlating positively with the expression of key glycolytic genes. Cellular experiments confirmed that HMMR knockdown notably suppressed aerobic glycolysis in LUAD cells. Moreover, overexpression of HMMR could further enhance the stemness and cisplatin resistance of LUAD cells by stimulating glycolysis. In brief, this study has validated that high levels of HMMR in LUAD are predictive of poor patient prognosis, and that overexpression of HMMR can catalyze aerobic glycolysis, thus promoting stemness and chemoresistance in LUAD cells. Thus, HMMR could be a target for improving chemosensitivity in LUAD.

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키워드

Adenocarcinoma of lung Drug resistance neoplasm Glycolysis Hyaluronan receptors Neoplastic stem cells