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LncRNA SNHG12 Decreases Non-Small Cell Lung Cancer Cell Sensitivity to Cisplatin by Repressing miR-525-5p and
Deli Tan1, Song Wang1, Peng Zhang1
1Department of Thoracic Surgery, Southwest Hospital, Chongqing Ninth People's Hospital, Chongqing, China.
Objective:
Non-small cell lung cancer (NSCLC) is recognized as one of the primary causes of global cancer-related mortality. Long noncoding RNAs (lncRNAs) participate in NSCLC cell progression. This study probed the potential mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in cisplatin (DDP)-resistance in NSCLC cells.
Methods:
The intracellular expressions of SNHG12, miR-525-5p, and XIAP were examined via reverse-transcription quantitative polymerase chain reaction (RT-qPCR). Afterwards, small interfering RNAs (siRNAs) of SNHG12, microRNA (miR)-525-5p inhibitor, and X-linked inhibitor of apoptosis (XIAP) pcDNA3.1 were transfected into NSCLC cells. Subsequently, changes in half-maximal (50%) inhibitory concentration (IC50) of NSCLC cells to DDP were detected through the cell counting kit-8 (CCK-8) method. NSCLC proliferative ability and apoptosis rate were determined with the help of colony formation and flow cytometry assays. The subcellular localization of SNHG12 was analyzed by nuclear/cytosol fractionation assay and binding relationships between miR-525-5p and SNHG12 or XIAP were analyzed via dual-luciferase reporter gene assay. Furthermore, rescue experiments were designed to detect the effects of miR-525-5p and XIAP on NSCLC sensitivity to DDP.
Results:
SNHG12 and XIAP were up-regulated in NSCLC cells while miR-525-5p was down-regulated. After DDP treatment and SNHG12 repression, NSCLC proliferative ability was decreased whereas apoptosis rate was increased, and NSCLC sensitivity to DDP was enhanced. Mechanically, SNHG12 repressed miR-525-5p expression, and miR-525-5p could targeted inhibit XIAP transcription level. miR-525-5p repression or XIAP overexpression reduced NSCLC sensitivity to DDP.
Conclusion:
SNHG12 was overexpressed in NSCLC cells and promoted XIAP transcription by repressing miR-525-5p expression, enhancing DDP-resistance in NSCLC cells.
Insights
Long noncoding RNA SNHG12 promotes cisplatin resistance in non-small cell lung cancer by upregulating XIAP via inhibiting miR-525-5p. This finding offers potential therapeutic targets for overcoming drug resistance in NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
- Long noncoding RNAs (lncRNAs) play a role in NSCLC progression and drug resistance.
- Understanding the mechanisms of cisplatin resistance is crucial for improving NSCLC treatment outcomes.
Purpose of the Study:
- To investigate the role of lncRNA SNHG12 in cisplatin (DDP) resistance in NSCLC cells.
- To elucidate the underlying molecular mechanism involving miR-525-5p and XIAP.
- To explore potential therapeutic strategies targeting the SNHG12/miR-525-5p/XIAP axis.
Main Methods:
- Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) to measure gene expression.
- Cell counting kit-8 (CCK-8), colony formation, and flow cytometry assays to assess cell viability, proliferation, and apoptosis.
- Transfection of small interfering RNAs (siRNAs), microRNA inhibitors, and plasmids.
- Dual-luciferase reporter gene assays to confirm binding interactions.
- Nuclear/cytosol fractionation to determine subcellular localization.
Main Results:
- SNHG12 and XIAP were upregulated, while miR-525-5p was downregulated in NSCLC cells.
- SNHG12 knockdown enhanced DDP sensitivity by increasing apoptosis and decreasing proliferation.
- SNHG12 directly repressed miR-525-5p, which in turn targeted and inhibited XIAP.
- Overexpression of XIAP or inhibition of miR-525-5p conferred DDP resistance.
Conclusions:
- SNHG12 promotes DDP resistance in NSCLC by upregulating XIAP through the repression of miR-525-5p.
- The SNHG12/miR-525-5p/XIAP axis is a key regulator of DDP resistance in NSCLC.
- Targeting this axis may represent a promising therapeutic strategy for overcoming DDP resistance in NSCLC.
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