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. 2025 Jan;15(1):7.
doi: 10.1007/s13205-024-04161-w. Epub 2024 Dec 12.

POU4F1 enhances lung cancer gemcitabine resistance by regulating METTL3-dependent TWF1 mRNA N6 adenosine methylation

Jianfeng Tang  1 , Zhijian Liu  1 , Guanghui Xie  1 , Chenbin Wang  1 , Yongjun Jiang  1
Affiliations

POU4F1 enhances lung cancer gemcitabine resistance by regulating METTL3-dependent TWF1 mRNA N6 adenosine methylation

Jianfeng Tang et al. 3 Biotech. 2025 Jan.

Abstract

This study aimed to investigate the role of POU Class 4 Homeobox 1 (POU4F1) in regulating gemcitabine (GEM) resistance in lung cancer cells. The mRNA and protein expressions were assessed using RT-qPCR, western blot, immunofluorescence, and immunohistochemistry. Cell viability and proliferation were assessed by CCK-8 assay and EdU assay. TUNEL staining and flow cytometry were employed to detect cell apoptosis. The m6A modification of TWF1 was detected using MeRIP assay. The interactions between molecules were validated using dual luciferase reporter gene, ChIP, and RIP assays. POU4F1 knockdown inhibited GEM resistance and autophagy in lung cancer cells. Mechanistically, POU4F1 transcriptionally activated methyltransferase-like protein 3 (METTL3) in GEM-resistant cells by binding to the METTL3 promoter. METTL3 promoted the N6-methyladenosine (m6A) modification and expression level of twinfilin-1 (TWF1). Overexpression of METTL3 and TWF1 weakened the effects of POU4F1 knockdown on GEM resistance and autophagy. Moreover, knockdown POU4F1 also enhanced GEM anti-tumor sensitivity in vivo. In conclusion, POU4F1 upregulation promoted GEM resistance in lung cancer cells by promoting autophagy through increasing METTL3-mediated TWF1 m6A modification.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04161-w.

Keywords: Gemcitabine resistance; Lung cancer; METTL3; POU4F1; TWF1.

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Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

References

    1. Allahyari M, Motavalizadeh-Kakhky AR, Mehrzad J, Zhiani R, Chamani J (2024) Cellulose nanocrystals derived from chicory plant: an un-competitive inhibitor of aromatase in breast cancer cells via PI3K/AKT/mTOP signalling pathway. J Biomol Struct Dyn 42(11):5575–5589. 10.1080/07391102.2023.2226751 - PubMed
    1. An Y, Duan H (2022) The role of m6A RNA methylation in cancer metabolism. Mol Cancer 21(1):14. 10.1186/s12943-022-01500-4 - PMC - PubMed
    1. Basu AK (2018) DNA damage, mutagenesis and cancer. Int J Mol Sci. 10.3390/ijms19040970 - PMC - PubMed
    1. Bohlen J, Roiuk M, Neff M, Teleman AA (2023) PRRC2 proteins impact translation initiation by promoting leaky scanning. Nucleic Acids Res 51(7):3391–3409. 10.1093/nar/gkad135 - PMC - PubMed
    1. Cao W, Gao J, Zhang Y, Li A, Yu P, Cao N, Liang J, Tang X (2022) Autophagy up-regulated by MEK/ERK promotes the repair of DNA damage caused by aflatoxin B1. Toxicol Mech Methods 32(2):87–96. 10.1080/15376516.2021.1968985 - PubMed

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