HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway

Jing Ji; Yasong Wang; Aixin Jing; Ling Ma; Jiayan Yang; Dexu Ren; Jinyu Lv; Mingxiao Lv; Menghan Xu; Qing Yuan; Xinhui Ma; Qilan Qian; Weiling Wang; Ting Geng; Yuanyuan Ding; Jingting Qin; Yuanyuan Liu; Jiaojiao Zhou; Lingyi Zuo; Shaojie Ma; Xiujun Wang; Bin Liu

doi:10.1016/j.heliyon.2024.e28440

HIF1A-dependent overexpression of MTFP1 promotes lung squamous cell carcinoma development by activating the glycolysis pathway

Heliyon. 2024 Mar 21;10(7):e28440. doi: 10.1016/j.heliyon.2024.e28440. eCollection 2024 Apr 15.

Authors

Jing Ji¹, Yasong Wang¹, Aixin Jing¹, Ling Ma¹, Jiayan Yang¹, Dexu Ren¹, Jinyu Lv¹, Mingxiao Lv¹, Menghan Xu¹, Qing Yuan¹, Xinhui Ma¹, Qilan Qian¹, Weiling Wang¹, Ting Geng¹, Yuanyuan Ding¹, Jingting Qin¹, Yuanyuan Liu¹, Jiaojiao Zhou¹, Lingyi Zuo¹, Shaojie Ma¹, Xiujun Wang¹, Bin Liu¹

Affiliation

¹ Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.

Abstract

Introduction: Mitochondrial fission process 1 (MTFP1) is an inner mitochondrial membrane (IMM) protein implicated in the development and progression of various tumors, particularly lung squamous cell carcinoma (LUSC). This study aims to provide a more theoretical basis for the treatment of LUSC.

Methods: Through bioinformatics analysis, MTFP1 was identified as a novel target gene of HIF1A. MTFP1 expression in LUSC was examined using The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Proteomics Data Commons (PDC) databases. The Kaplan-Meier plotter (KM plotter) database was utilized to evaluate its correlation with patient survival. Western blot and chromatin immunoprecipitation (ChIP) assays were employed to confirm the regulatory relationship between MTFP1 and HIF1A. Additionally, cell proliferation, colony formation, and migration assays were conducted to investigate the mechanism by which MTFP1 enhances LUSC cell proliferation and metastasis.

Results: Our findings revealed that MTFP1 overexpression correlated with poor prognosis in LUSC patients(P < 0.05). Moreover, MTFP1 was closely associated with hypoxia and glycolysis in LUSC (R = 0.203; P < 0.001, R = 0.391; P < 0.001). HIF1A was identified as a positive regulator of MTFP1. Functional enrichment analysis demonstrated that MTFP1 played a role in controlling LUSC cell proliferation. Cell proliferation, colony formation, and migration assays indicated that MTFP1 promoted LUSC cell proliferation and metastasis by activating the glycolytic pathway (P < 0.05).

Conclusions: This study establishes MTFP1 as a novel HIF1A target gene that promotes LUSC growth by activating the glycolytic pathway. Investigating MTFP1 may contribute to the development of effective therapies for LUSC patients, particularly those lacking targeted oncogene therapies.

Keywords: Glycolysis; HIF1A; Lung squamous cell carcinoma; MTFP1; Migration; Proliferation.