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.

Cells
|August 12, 2022
PubMed

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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