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LINC00511 Knockdown Suppresses Resistance to Cisplatin in Lung Adenocarcinoma by Interacting with miR-182-3p and BIRC5

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Abstract

We studied the role of long intergenic non-protein coding RNA 00,511 (LINC00511) in lung adenocarcinoma (LUAD), with a specific focus on acquired chemoresistance. LINC00511 expression was higher in responders to cisplatin (DDP, another name for cisplantin) than non-responders, in A549/DDP cells than in parental A549 cells and normal human bronchial epithelial cells (16HBE). LINC00511 knockdown decreased the half maximal inhibitory concentration (IC50) value, suppressed A549/DDP cell viability, but induced apoptosis. LINC00511 bound with miR-182 and increased the expression of baculoviral inhibitor of apoptosis protein (IAP) repeat containing 5 (BIRC5). BIRC5 knockdown mimicked the effects of LINC00511 knockdown on the IC50 value, A549/DDP cell viability, and apoptosis. BIRC5 overexpression negated the effects of LINC00511 knockdown on A549/DDP cells. In vivo, LINC00511 knockdown attenuated the tumorigenesis of A549/DDP cells after DDP injection. These results provide a novel LINC00511/miR-182/BIRC5 paradigm to explain the mechanism of acquired DDP resistance.

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Abbreviations

ceRNA:

Competitive endogenous RNA

ECL:

Enhanced chemiluminescence

EGFR:

Epidermal growth factor receptor

FBS:

Fetal bovine serum

IC50:

Inhibitory concentration

LncRNAs:

Long non-coding RNAs

LUAD:

Lung adenocarcinoma

miRNA:

MicroRNA

PBS:

Phosphate buffer solution

PI:

Propidium iodide

PVDF:

Poly (vinylidene fluoride)

RECIST:

Response evaluation criteria in solid tumors

SPF:

Specific pathogen-free

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Acknowledgements

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Funding

This study was funded by the Cangzhou City Key Research and Development Plan Guidance Project Task Book (183302108).

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ZCZ is responsible for the guarantor of integrity of the entire study, study concepts & design, definition of intellectual content, literature research, clinical studies, experimental studies, data analysis; YFS is responsible for the study concepts & design, clinical studies, data acquisition, statistical analysis, manuscript editing; XYG is responsible for the statistical analysis, manuscript editing; JL is responsible for the definition of intellectual content, experimental studies, data acquisition & analysis, manuscript preparation; MYZ is responsible for the definition of intellectual content, clinical studies, experimental studies, manuscript preparation & review. All authors read and approved the final manuscript.

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Correspondence to Zhongcheng Zhu.

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The study was approved by the Cangzhou Central Hospital (No.2017–008-01).

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Zhu, Z., Shi, Y., Gong, X. et al. LINC00511 Knockdown Suppresses Resistance to Cisplatin in Lung Adenocarcinoma by Interacting with miR-182-3p and BIRC5. Mol Biotechnol 64, 252–262 (2022). https://doi.org/10.1007/s12033-021-00400-0

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  • DOI: https://doi.org/10.1007/s12033-021-00400-0

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