Knockdown of LINC00511 enhances radiosensitivity of lung adenocarcinoma via regulating miR-497-5p/SMAD3

Li, Chongxin; Fu, Yanyan; He, Yongmei; Huang, Nan; Yue, Jun; Miao, Yi; Lv, Jialing; Xiao, Youchuan; Deng, Ruoyu; Zhang, Chao; Huang, Meifang

doi:10.1080/15384047.2023.2165896

Cited by 6 publications

(1 citation statement)

References 33 publications

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“…Notably, aberrant genomic DNA methylation in NSCLC tumor-associated fibroblasts is a critical regulator of tumor progression, with SMAD3 promoter hypermethylation associated with reduced gene expression [ 41 ]. Evidence suggests that inhibiting SMAD3 in CAFs diminishes its activation and secretion of extracellular matrix components, thereby curtailing tumor cell survival and enhancing radiosensitivity [ 42 ]. Thus, strategies to inhibit SMAD3 activity in CAFs may present a novel approach to augment radiotherapy efficacy in NSCLC and improve patient clinical prognosis [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer

Han,

Chen,

Zhang

et al. 2024

J Transl Med

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Objective Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. Methods The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models. Results Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway. Conclusion High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer

Han,

Chen,

Zhang

et al. 2024

J Transl Med

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Matrine alkaloids modulating DNA damage repair in chemoresistant non-small cell lung cancer cells

Wang,

Liu,

Liao

et al. 2024

BMC Cancer

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Background Non-small cell lung cancer (NSCLC) presents a significant challenge in the medical field due to its high incidence and resistance to chemotherapy. Chemoresistance in NSCLC diminishes treatment efficacy and contributes to poor patient outcomes. Matrine alkaloids have shown promise in reversing chemotherapy resistance in NSCLC by targeting DNA repair mechanisms. Methods Utilizing molecular dynamics simulations, we explored the interactions between Matrine alkaloids and DNA repair-related proteins to elucidate their impact on NSCLC cells. In vitro experiments involved treating A549/DDP cells with Matrine alkaloids to evaluate their sensitizing effects on lung cancer cells. Additionally, animal model experiments were conducted to validate the therapeutic potential of Matrine alkaloids in NSCLC treatment. Results Our findings demonstrate that Matrine alkaloids disrupt DNA damage repair processes in NSCLC cells, leading to increased sensitivity to chemotherapy. Molecular docking studies revealed the intricate mechanisms by which Matrine alkaloids interact with DNA repair proteins, impacting cell survival and proliferation. Both cell experiments and animal models confirmed the chemosensitizing effects of Matrine alkaloids in NSCLC treatment. Conclusion Matrine alkaloids offer a promising avenue for overcoming chemotherapy resistance in NSCLC by interfering with DNA repair pathways. This study lays a solid foundation for future clinical investigations into the potential of Matrine alkaloids as effective therapeutic agents for enhancing NSCLC treatment outcomes. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-024-12991-3.

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linc00511 Knockdown Inhibits Lung Cancer Progression by Regulating miR-16-5p/MMP11

Song

Luo

et al. 2023

Crit Rev Eukaryot Gene Expr

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Lung cancer (LC) is a malignant tumor that extremely impairs people. According to numerous studies, long non-coding RNA (lncRNA) was inextricably involved in the advancement of LC. The work aspired to identify linc00511 expression in LC and to dig for the underlying mechanisms linc00511 regulated LC progression. Experimental outcomes revealed that linc00511 was obviously upregulated in LC, and linc00511 knockdown significantly impaired the malignant phenotype of LC cells <i>in vitro</i>. For an in-depth study on the contribution of linc00511 to LC advancement, it was disclosed that miR-16-5p had binding sites to the sequence of linc00511, which also inversely affected linc00511 expression in LC. Further experimental data demonstrated that miR-16-5p directly and negatively targeted matrix metallopeptidase 11 (MMP11). Also, rescue experiments displayed that miR-16-5p inhibition or MMP11 overexpressing offset the suppressive impacts of linc00511 silencing on LC progression. To sum up, our findings indicated that linc00511 performed a crucial role in facilitating LC progression, and mechanistic studies demonstrated that linc00511 aggravated LC progression via targeting the miR-16-5p/MMP11 axis.

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Knockdown of LINC00511 enhances radiosensitivity of lung adenocarcinoma via regulating miR-497-5p/SMAD3

Cited by 6 publications

References 33 publications

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer

Single-cell transcriptomic sequencing data reveal aberrant DNA methylation in SMAD3 promoter region in tumor-associated fibroblasts affecting molecular mechanism of radiosensitivity in non-small cell lung cancer

Matrine alkaloids modulating DNA damage repair in chemoresistant non-small cell lung cancer cells

linc00511 Knockdown Inhibits Lung Cancer Progression by Regulating miR-16-5p/MMP11

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