METTL3-mediated m6A modification of circ_0000620 regulates cisplatin sensitivity and apoptosis in lung adenocarcinoma via the MiR-216b-5p/ KRAS axis

被引:2
|
作者
Li, Xiangmei [1 ]
Wang, Yinlu [1 ]
Cheng, Jiuling [1 ]
Qiu, Liliang [1 ]
Wang, Ruiyang [1 ]
Zhang, Yuping [1 ]
Wang, Huaqi [1 ]
机构
[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Resp Med, Zhengzhou 450000, Peoples R China
基金
中国国家自然科学基金;
关键词
Lung adenocarcinoma; circ_0000620; METTL3; miR-216b-5p; KRAS; RESISTANCE; CANCER; CIRCRNA; CELLS; RNAS;
D O I
10.1016/j.cellsig.2024.111349
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Circular RNAs (circRNAs) are stable non-coding RNAs characterized by the absence of the conventional 5 ' cap and 3 ' polyadenylated tail structure. Its involvement in various aspects of cancers underscores its significance in oncology. Elevated expression of circ_0000620 was observed in both lung adenocarcinoma (LUAD) tissues and cell lines. In vitro, experiments demonstrated that the downregulation of circ_0000620 increased cisplatin sensitivity and promoted cell apoptosis while suppressing malignant characteristics such as cell migration and proliferation. Further investigation into the mechanism underlying the increased expression of circ_0000620 revealed that Methyltransferase 3, N6-Adenosine-Methyltransferase Complex Catalytic Subunit (METTL3) mediates the m6A methylation modification of circ_0000620, thereby promoting its stability and expression. Furthermore, circ_0000620 modulates the miR-216b-5p/KRAS axis to influence apoptosis and cisplatin sensitivity in both A549 and H1299 cell lines. These findings were corroborated by in vivo nude mouse experiments, which showed that knockdown of circ_0000620 inhibited tumor growth and proliferation. In summary, METTL3 plays a role in regulating the stability of circ_0000620 expression, and circ_0000620 exerts its effects on LUAD apoptosis and cisplatin sensitivity through the miR-216b-5p/KRAS signaling pathway.
引用
收藏
页数:12
相关论文
共 50 条
  • [41] METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis
    Fan, Hui-Ning
    Chen, Zhao-Yu
    Chen, Xiao-Yu
    Chen, Ming
    Yi, You-Cai
    Zhu, Jin-Shui
    Zhang, Jing
    MOLECULAR CANCER, 2022, 21 (01)
  • [42] METTL14-mediated m6A modification of circORC5 suppresses gastric cancer progression by regulating miR-30c-2-3p/AKT1S1 axis
    Hui-Ning Fan
    Zhao-Yu Chen
    Xiao-Yu Chen
    Ming Chen
    You-Cai Yi
    Jin-Shui Zhu
    Jing Zhang
    Molecular Cancer, 21
  • [43] WTAP-Mediated m6A RNA Methylation Regulates the Differentiation of Bone Marrow Mesenchymal Stem Cells via the miR-29b-3p/HDAC4 Axis
    Liu, Jincheng
    You, Yunhao
    Sun, Zhenqian
    Zhang, Lu
    Li, Xiang
    Dai, Zihan
    Ma, Jinlong
    Chen, Yunzhen
    Jiao, Guangjun
    STEM CELLS TRANSLATIONAL MEDICINE, 2023, 12 (05) : 307 - 321
  • [44] Exosomal miR-130a-3p confers cisplatin resistance in esophageal cancer by regulating ferroptosis via the suppression of METTL14-mediated m6A RNA methylation of FSP1
    Han, Hu
    Li, Yan
    Lin, Zhiyi
    Ma, Xiaoping
    Huang, Wukui
    Lu, Cengceng
    Ma, Rongyan
    Han, Rui
    INTERNATIONAL IMMUNOPHARMACOLOGY, 2025, 146
  • [45] miR-340-3p-modified bone marrow mesenchymal stem cell-derived exosomes inhibit ferroptosis through METTL3-mediated m6A modification of HMOX1 to promote recovery of injured rat uterus
    Xiao, Bang
    Zhu, Yiqing
    Liu, Meng
    Chen, Meiting
    Huang, Chao
    Xu, Dabing
    Wang, Fang
    Sun, Shuhan
    Huang, Jinfeng
    Sun, Ningxia
    Yang, Fu
    STEM CELL RESEARCH & THERAPY, 2024, 15 (01)
  • [46] HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis
    Li, Ke
    Gong, Quan
    Xiang, Xu-Dong
    Guo, Gang
    Liu, Jia
    Zhao, Li
    Li, Jun
    Chen, Nan
    Li, Heng
    Zhang, Li-Juan
    Zhou, Chun-Yan
    Wang, Zhi-Yong
    Zhuang, Li
    JOURNAL OF TRANSLATIONAL MEDICINE, 2023, 21 (01)
  • [47] HNRNPA2B1-mediated m6A modification of lncRNA MEG3 facilitates tumorigenesis and metastasis of non-small cell lung cancer by regulating miR-21-5p/PTEN axis
    Ke Li
    Quan Gong
    Xu-Dong Xiang
    Gang Guo
    Jia Liu
    Li Zhao
    Jun Li
    Nan Chen
    Heng Li
    Li-Juan Zhang
    Chun-Yan Zhou
    Zhi-Yong Wang
    Li Zhuang
    Journal of Translational Medicine, 21
  • [48] CircUGGT2 downregulation by METTL14-dependent m6A modification suppresses gastric cancer progression and cisplatin resistance through interaction with miR-186-3p/MAP3K9 axis
    Chen, Xiao-Yu
    Yang, Yan-Ling
    Yu, Yi
    Chen, Zhao-Yu
    Fan, Hui-Ning
    Zhang, Jing
    Zhu, Jin-Shui
    PHARMACOLOGICAL RESEARCH, 2024, 204
  • [49] MiR-124-3p inhibits cell stemness in glioblastoma via targeting EPHA2 through ALKBH5-mediated m6A modification
    Tuoheti, Maimaitiyiming
    Li, Jinxian
    Zhang, Cheng
    Gao, Feng
    Wang, Jichao
    Wu, Yonggang
    HUMAN CELL, 2024, 38 (01)
  • [50] EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway
    Xinyu Yang
    Fengjiao Han
    Xiang Hu
    Guosheng Li
    Hanyang Wu
    Can Can
    Yihong Wei
    Jinting Liu
    Ruiqing Wang
    Wenbo Jia
    Chunyan ji
    Daoxin Ma
    Biomarker Research, 11