Abstract
Long noncoding RNA LINC00482 (LINC00482) is dysregulated in non-small cell lung cancer cells (NSCLC). Herein, this research examined the actions and specific mechanisms of LINC00482 in cisplatin (DDP) resistance in NSCLC. LINC00482 expression was assessed using RT-qPCR in clinical NSCLC tissues and cell lines. Knockdown and ectopic expression assays were conducted in A549 and HCC44 cells, followed by determination of cell proliferation with CCK-8 and clone formation assays, apoptosis with flow cytometry, and DDP sensitivity. The association between LINC00482, E2F1, and CLASRP was evaluated with dual-luciferase reporter, ChIP, and RIP assays. The role of LINC00482 in NSCLC was confirmed in nude mice. NSCLC tissues and cells had upregulated LINC00482 expression. LINC00482 was mainly localized in the cell nucleus, and LINC00482 recruited E2F1 to enhance CLASRP expression in NSCLC cells. LINC00482 knockdown enhanced the DDP sensitivity and apoptosis of NSCLC cells while reducing cell proliferation, which was negated by overexpressing CLASRP. LINC00482 knockdown restricted tumor growth and enhanced DDP sensitivity in NSCLC in vivo. LINC00482 silencing downregulated CLASRP through E2F1 to facilitate the sensitivity to DDP in NSCLC.
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Data availability
The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.
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Thanks for the grant from the Affiliated Hospital of Guangdong Medical University Clinical Research Project in Hospital Fund (No. LCYJ2021B005).
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LYM conceived the ideas. LYM, LJM and LSJ designed the experiments. LYM, LJM, LSJ, CYT and LYP performed the experiments. LYM, LJM and LSJ analyzed the data. LYM, YZX and WYC provided critical materials. LYM, CYT and LYP wrote the manuscript. YZX and WYC supervised the study. All the authors have read and approved the final version for publication.
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10142_2023_1260_MOESM1_ESM.tif
Supplementary file1 Supplementary figure 1. Overexpression of LINC00482 restrains the sensitivity of NSCLC cells to DDP. Notes: A: RT-qPCR to assess the transfection efficiency of oe-LINC00482. B: CCK-8 assay to detect the viability of A549 and HCC44 cells upon 48-h stimulation with different concentrations of DDP. C: Half inhibition concentration (IC50) of DDP in A549 and HCC44 cells. D: Clone formation assay to detect the clonogenicity of A549 cells. E: Flow cytometry to detect apoptosis in A549 cells. The measurement data were displayed as mean ± standard error of mean. Comparisons between the two groups were performed using unpaired t-test. * indicates P < 0.05 compared with the oe-NC group, N = 3. (TIF 23250 KB)
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Lin, Y., Li, J., Li, S. et al. Long noncoding RNA LINC00482 silencing sensitizes non-small cell lung cancer cells to cisplatin by downregulating CLASRP via E2F1. Funct Integr Genomics 23, 335 (2023). https://doi.org/10.1007/s10142-023-01260-4
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DOI: https://doi.org/10.1007/s10142-023-01260-4