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Whole Transcriptome Analysis Identifies Platycodin D-Mediated RNA Regulatory Network in Non-Small-Cell Lung Cancer
Shuyu Zheng1,2,3, Zejuan Xie1, Yanlin Xin1
1Department of Biochemistry and Molecular Biology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Abstract:
Non-small-cell lung cancer (NSCLC) is one of the most fatal malignant tumors harmful to human health. Previous studies report that Platycodin D (PD) exhibits anti-tumor effects in multiple human cancers, including NSCLC, but the underlying mechanisms are largely unknown. Accumulating evidence indicates that non-coding RNAs (ncRNAs) participate in NSCLC disease progression, but the link between PD and the ncRNAs in NSCLC is poorly elucidated. Here, we used whole transcriptome sequencing to systematically investigate the RNAs-associated regulatory network in the PD treating NSCLC cell lines. A total of 942 significantly dysregulated RNAs were obtained. Among those, five circRNAs and six IncRNAs were rigorously selected via database and in vitro validation. In addition, the functional enrichment study of differentially expressed mRNAs, single nucleotide polymorphisms (SNPs) within PD-related mRNA structures, and the interaction between PD and mRNA-related proteins were analyzed through gene set enrichment analysis (GSEA), structural variant analysis, and molecular docking, respectively. With further in vitro validation, the results show that PD inhibits cell proliferation, arrests the cell cycle, and induces cell apoptosis through targeting BCL2-related proteins. We hope these data can provide a full concept of PD-related molecular changes, leading to a new treatment for NSCLC.
Insights
Platycodin D (PD) shows anti-tumor effects in non-small-cell lung cancer (NSCLC) by regulating RNA networks. This study reveals PD inhibits NSCLC cell growth and induces apoptosis by targeting BCL2 proteins, offering new therapeutic insights.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Non-small-cell lung cancer (NSCLC) is a leading cause of cancer-related mortality.
- Platycodin D (PD) demonstrates anti-tumor properties in various cancers, but its mechanisms in NSCLC are unclear.
- Non-coding RNAs (ncRNAs) are implicated in NSCLC progression, yet their interaction with PD remains poorly understood.
Purpose of the Study:
- To investigate the RNA regulatory network influenced by Platycodin D (PD) in non-small-cell lung cancer (NSCLC) cells.
- To identify specific non-coding RNAs (circRNAs and lncRNAs) and messenger RNAs (mRNAs) affected by PD treatment.
- To elucidate the molecular mechanisms underlying PD's anti-cancer effects in NSCLC.
Main Methods:
- Whole transcriptome sequencing was employed to analyze RNA expression profiles in PD-treated NSCLC cell lines.
- Bioinformatic analyses, including functional enrichment (GSEA), structural variant analysis, and molecular docking, were performed.
- In vitro validation was conducted to confirm the roles of selected RNAs and PD's effects on cellular processes and protein targets.
Main Results:
- Whole transcriptome sequencing identified 942 significantly dysregulated RNAs, including five circRNAs and six lncRNAs.
- Functional enrichment analysis, structural variant analysis, and molecular docking provided insights into PD's molecular interactions.
- In vitro studies confirmed that PD inhibits NSCLC cell proliferation, induces cell cycle arrest, and promotes apoptosis by targeting BCL2-related proteins.
Conclusions:
- Platycodin D (PD) modulates a complex RNA regulatory network in non-small-cell lung cancer (NSCLC).
- PD exerts anti-cancer effects by inhibiting proliferation, arresting the cell cycle, and inducing apoptosis via BCL2 targeting.
- These findings provide a comprehensive understanding of PD's molecular actions and suggest its potential as a novel therapeutic agent for NSCLC.
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