Whole Transcriptome Analysis Identifies Platycodin D-Mediated RNA Regulatory Network in Non–Small-Cell Lung Cancer

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.

The pharmacology and mechanisms of platycodin D, an active triterpenoid saponin from Platycodon grandiflorus

“…And this effect should be correlated with cholesterol ( Bailly and Vergoten, 2020 ). Zheng et al (2022) also identified the PD-mediated RNA regulatory network in NSCLC through the whole transcriptome analysis. That is to say, PD inhibits cell proliferation, arrests the cell cycle, and induces cell apoptosis through targeting BCL2-related proteins.…”

Platycodin D inhibits angiogenic vascular mimicry in NSCLC by regulating the eIF4E-mediated RNA methylome

“…As a traditional herbal medicine, platycodin D (PD) is the major bioactive monomer derived from Platycodon grandiflorum (P. grandiflorum) and is used as an expectorant for pulmonary disease in Asia [ 2 ]. We previously found that PD exhibits anticancer effects on NSCLC through noncoding RNA (ncRNA) regulation [ 3 ]. Although the RNA methylome is a hotspot in ncRNA regulation studies, especially for N 7 -methylguanosine (m 7 G) modification, in-depth pharmacological studies related to this topic are limited [ 4 ].…”