KT2440-induced RBM47 regulates non-small cell lung cancer stem cell properties and T cell-mediated antitumor activity.
[BACKGROUND] Lung cancer (LC) remains a major cause of cancer-related mortality globally and is the most frequently diagnosed malignancy.
APA
Zheng QX, Guo BL, et al. (2025). KT2440-induced RBM47 regulates non-small cell lung cancer stem cell properties and T cell-mediated antitumor activity.. Journal of thoracic disease, 17(11), 10445-10458. https://doi.org/10.21037/jtd-2025-1945
MLA
Zheng QX, et al.. " KT2440-induced RBM47 regulates non-small cell lung cancer stem cell properties and T cell-mediated antitumor activity.." Journal of thoracic disease, vol. 17, no. 11, 2025, pp. 10445-10458.
PMID
41376900
Abstract
[BACKGROUND] Lung cancer (LC) remains a major cause of cancer-related mortality globally and is the most frequently diagnosed malignancy. Recent research has highlighted the role of intratumor microbiota in cancer pathogenesis. Studies have indicated a close association of strain KT2440 with non-small cell LC (NSCLC) progression. However, the underlying mechanism of KT2440-induced NSCLC tumorigenesis is unknown. In this study, we aimed to investigate how KT2440 influences non-small cell lung cancer stem cell (NSCL-CSC) properties and T cell-mediated antitumor activity.
[METHODS] RNA-binding motif protein 47 (RBM47) expression in NSCLC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR). N-methyladenosine (mA) modification of RBM47 was examined via methylated RNA immunoprecipitation (RIP)-PCR. and experiments were used to assess the effect of RBM47 on cancer stem cell (CSC) growth.
[RESULTS] These experiments revealed that the KT2440 induced mA, which enhanced the messenger RNA (mRNA) expression of RBM47, whereas methyltransferase-like 3 (METTL3) and YTHDF1-dependent mA methylation decreased RBM47 expression in NSCLC. RBM47 was found to be downregulated in CSCs. Furthermore, it was found that RBM47 knockdown (KD) increased the self-renewal and tumorigenesis ability of NSCL-CSCs likely via the Wnt pathway. Moreover, RBM47 enhanced T-cell proliferation and cytotoxicity by destabilizing the programmed death-ligand 1 (PD-L1) mRNA via 3'-untranslated region (3'-UTR) binding.
[CONCLUSIONS] The RBM47 induction pathway, influenced by KT2440-induced m6A modification, modulates NSCL-CSC properties and T cell-mediated antitumor activity, supporting RBM47 as a novel therapeutic target against LC.
[METHODS] RNA-binding motif protein 47 (RBM47) expression in NSCLC tumor samples and cell lines was examined via quantitative real-time polymerase chain reaction (qRT-PCR). N-methyladenosine (mA) modification of RBM47 was examined via methylated RNA immunoprecipitation (RIP)-PCR. and experiments were used to assess the effect of RBM47 on cancer stem cell (CSC) growth.
[RESULTS] These experiments revealed that the KT2440 induced mA, which enhanced the messenger RNA (mRNA) expression of RBM47, whereas methyltransferase-like 3 (METTL3) and YTHDF1-dependent mA methylation decreased RBM47 expression in NSCLC. RBM47 was found to be downregulated in CSCs. Furthermore, it was found that RBM47 knockdown (KD) increased the self-renewal and tumorigenesis ability of NSCL-CSCs likely via the Wnt pathway. Moreover, RBM47 enhanced T-cell proliferation and cytotoxicity by destabilizing the programmed death-ligand 1 (PD-L1) mRNA via 3'-untranslated region (3'-UTR) binding.
[CONCLUSIONS] The RBM47 induction pathway, influenced by KT2440-induced m6A modification, modulates NSCL-CSC properties and T cell-mediated antitumor activity, supporting RBM47 as a novel therapeutic target against LC.