FOXA2 Activates RND1 to Regulate Arachidonic Acid Metabolism Pathway and Suppress Cisplatin Resistance in Lung Squamous Cell Carcinoma

被引:0
|
作者
Zhou, Yafu [1 ]
Chen, Huiguo [1 ]
Yan, Jianhua [1 ]
Yao, Qi [1 ]
Kong, Chunchu [2 ]
Peng, You [3 ]
Xiao, Shengying [4 ]
Yang, Jinsong [1 ]
机构
[1] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Thorac Surg, Affiliated Hosp 1, Changsha, Peoples R China
[2] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Radiol, Affiliated Hosp 1, Changsha, Peoples R China
[3] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Geriatr, Affiliated Hosp 1, Changsha, Peoples R China
[4] Hunan Normal Univ, Hunan Prov Peoples Hosp, Dept Oncol, Affiliated Hosp 1, Changsha, Peoples R China
来源
CLINICAL RESPIRATORY JOURNAL | 2024年 / 18卷 / 08期
基金
湖南省自然科学基金;
关键词
arachidonic acid; DDP resistance; lung squamous cell carcinoma; RND1; RHO-GTPASES; CANCER; EXPRESSION; PROMOTES; RAS;
D O I
10.1111/crj.13814
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
BackgroundThe primary cause of cancer-related fatalities globally is lung cancer. Although the chemotherapy drug cisplatin (DDP) has brought certain benefits to patients, the rapid development of drug resistance has greatly hindered treatment success.MethodsWe used the lung squamous cell carcinoma (LUSC) mRNA data set to explore the differentially expressed gene (RND1) in LUSC and detected RND1 expression in LUSC cells and DDP-resistant cells by qRT-PCR. Meanwhile, we performed abnormal expression treatment on RND1 and conducted CCK8, colony formation, and flow cytometry to evaluate the impact of RND1 expression on cell proliferation, apoptosis, and DDP resistance. In addition, we analyzed metabolism pathways involving RND1 using GSEA. We also used online tools such as hTFtarget and JASPAR to screen for the upstream transcription factor FOXA2 of RND1 and verified their relationship through CHIP and dual luciferase experiments. Finally, we validated the role of FOXA2-RND1 in DDP resistance in LUSC through the above experiments.ResultsRND1 was downregulated in LUSC, and overexpression of RND1 repressed proliferation and DDP resistance of LUSC cells and facilitated cell apoptosis. RND1 modulated the arachidonic acid (AA) metabolism pathway, and FOXA2 positively manipulated RND1 expression. By activating FOXA2, stabilizing RND1, and regulating AA levels, the sensitivity of LUSC cells to DDP could be enhanced.ConclusionOur study suggested that FOXA2 positively modulated the RND1-AA pathway, which repressed the resistance of LUSC cells to DDP. FOXA2 activates RND1 to suppress the arachidonic acid metabolism pathway and cisplatin resistance in lung squamous cell carcinoma.image
引用
收藏
页数:9
相关论文
共 50 条
  • [21] CDKN2A inhibited ferroptosis through activating JAK2/STAT3 pathway to modulate cisplatin resistance in cervical squamous cell carcinoma
    Yong, Xiang
    Zhang, Yanling
    Tang, Heng
    Hu, Huaiyuan
    Song, Rui
    Wu, Qiang
    ANTI-CANCER DRUGS, 2024, 35 (08) : 698 - 708
  • [22] Long non-coding RNA-neighboring enhancer of FOXA2 inhibits the migration and invasion of small cell lung carcinoma cells by downregulating transforming growth factor-1
    Wu, Lei
    Wang, Pan
    ONCOLOGY LETTERS, 2019, 17 (06) : 4969 - 4975
  • [23] HOXA1 silencing inhibits cisplatin resistance of oral squamous cell carcinoma cells via IκB/NF-κB signaling pathway
    Zhu, Ruifeng
    Mao, Yiting
    Xu, Xianzhi
    Li, Yingying
    Zheng, Jiwei
    ANTI-CANCER DRUGS, 2024, 35 (06) : 492 - 500
  • [24] TNFAIP2 confers cisplatin resistance in head and neck squamous cell carcinoma via KEAP1/NRF2 signaling
    Xu, Teng
    Yang, Yuemei
    Chen, Zhihong
    Wang, Jinsong
    Wang, Xiaolei
    Zheng, Yang
    Wang, Chao
    Wang, Yachen
    Zhu, Zaiou
    Ding, Xu
    Zhou, Junbo
    Li, Gang
    Zhang, Hongchuang
    Zhang, Wei
    Wu, Yunong
    Song, Xiaomeng
    JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2023, 42 (01)
  • [25] TNFAIP2 confers cisplatin resistance in head and neck squamous cell carcinoma via KEAP1/NRF2 signaling
    Teng Xu
    Yuemei Yang
    Zhihong Chen
    Jinsong Wang
    Xiaolei Wang
    Yang Zheng
    Chao Wang
    Yachen Wang
    Zaiou Zhu
    Xu Ding
    Junbo Zhou
    Gang Li
    Hongchuang Zhang
    Wei Zhang
    Yunong Wu
    Xiaomeng Song
    Journal of Experimental & Clinical Cancer Research, 42
  • [26] Methylseleninic acid activates Keap1/Nrf2 pathway via up-regulating miR-200a in human oesophageal squamous cell carcinoma cells
    Liu, Mei
    Hu, Chenfei
    Xu, Qing
    Chen, Lechuang
    Ma, Kai
    Xu, Ningzhi
    Zhu, Hongxia
    BIOSCIENCE REPORTS, 2015, 35
  • [27] TRIM27 Interacts with KLF12 to regulate L1CAM expression, influencing cisplatin resistance and cancer metastasis in esophageal squamous cell carcinoma
    Zhang, Hao
    Li, Chunxiang
    He, Jie
    CANCER RESEARCH, 2024, 84 (06)
  • [28] lncRNA SNHG26 promoted the growth, metastasis, and cisplatin resistance of tongue squamous cell carcinoma through PGK1/Akt/mTOR signal pathway
    Jiang, Qingkun
    Wang, Zhonghao
    Qi, Qi
    Li, Jialun
    Xin, Yuqi
    Qiu, Jiaxuan
    MOLECULAR THERAPY ONCOLYTICS, 2022, 24 : 355 - 370
  • [29] PER2 binding to PDK1 enhances the cisplatin sensitivity of oral squamous cell carcinoma through inhibition of the AKT/mTOR pathway
    Zheng, Hongyu
    Yu, Wenguang
    Ren, Jie
    Tang, Hong
    Li, Hengyan
    Zhang, Zhiwei
    Yin, Shilin
    Yang, Kai
    CELLULAR SIGNALLING, 2024, 122
  • [30] AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway
    Wei-Min Chang
    Yu-Chan Chang
    Yi-Chieh Yang
    Sze-Kwan Lin
    Peter Mu-Hsin Chang
    Michael Hsiao
    Journal of Experimental & Clinical Cancer Research, 38