|Table of Contents|

UCHL1 promotes the proliferation and metastasis of lung cancer cells by regulating glycolytic metabolism in tumor microenvironment

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2024 16
Page:
2975-2981
Research Field:
Publishing date:

Info

Title:
UCHL1 promotes the proliferation and metastasis of lung cancer cells by regulating glycolytic metabolism in tumor microenvironment
Author(s):
LI Aike; LIN Pingping; ZHAO Jiwei; GUO Yan; ZHANG Liguang; LI Fubo; DONG Yi; DU Xinsheng
Department of Oncology,Affiliated Hospital of Chengde Medical College,Hebei Chengde 067000,China.
Keywords:
lung cancer; ubiquitin C-terminal hydrolase-L1 (UCHL1); glycolysis; proliferation; metastasis
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2024.16.008
Abstract:
Objective:To explore the effect of ubiquitin C-terminal hydrolase-L1 (UCHL1) on the proliferation and metastasis of lung cancer cells by regulating hypoxia-inducible factor 1 (HIF-1) mediated metabolic reprogramming.Methods:Immunohistochemistry and real-time quantitative polymerase chain reaction were used to detect the expression of UCHL1 and HIF-1 in lung cancer tissues and cells.Kaplan-Meier Plotter and UALCAN databases analyzed the correlation between the expression levels of UCHL1 and HIF-1 and patient survival,and further analyzed their expression in tumor tissues of patients with different clinical pathological grades and lymphatic metastasis.Clone formation,migration,and invasion assessment of malignant biological behavior changes in lung cancer HCC4006 cells transfected with UCHL1 siRNA.Western Blot detection of the expression of IL-6/STAT3 markers in tumor cells after silencing UCHL1.Results:Immunohistochemistry,real-time quantitative polymerase chain reaction,and correlation analysis,the results showed that the expressions of UCHL1 and HIF-1 in lung cancer tissues and cells were significantly increased compared with those in adjacent tissues and normal bronchial epithelial cells,and the expression levels of the two were positively correlated (P＜0.01),and these results were consistent with the expression trend of UCHL1 and HIF-1 in Oncomine database.The results of bioinformatics analysis showed that the abnormally high expression of UCHL1 and HIF-1 was negatively correlated with the survival time of lung cancer patients,but positively correlated with the pathological grade and lymph node metastasis of patients (P＜0.01).The ability of colony formation,migration,and invasion of lung cancer HCC4006 cells transfected with UCHL1 siRNA was significantly reduced compared with the control cells,the oxygen consumption of the cells was significantly increased,and the LDH activity and LD secretion were inhibited (P＜0.01).Western Blot results showed that silencing UCHL1 inhibited HIF-1 expression and decreased the expression of tumor cell glycolysis IL-6/STAT3 signaling pathway biomarkers mediated by hypoxia (P＜0.01).Conclusion:Lung cancer cells acquire strong proliferative and metastatic phenotypes through metabolic reprogramming mediated by the UCHL1-HIF-1 axis,providing a rationale for therapies targeting this gene network.

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