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Systematic Transcriptome Analysis Reveals the Inhibitory Function of Cinnamaldehyde in Non-Small Cell Lung Cancer
1Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, China.
Abstract:
Cinnamaldehyde (CA) is the main component extracted from the traditional Chinese medicine cinnamon. Recent studies revealed that CA has antiviral and anti-tumor effects. However, the effect and mechanism of CA on non-small cell lung cancer (NSCLC) through whole transcriptome sequencing integrated analysis have not been systematically investigated. In this study, whole transcriptome sequencing was used to identify differentially expressed messenger RNAs (mRNAs), micro RNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were influenced by CA and screen regulatory pathways. The results showed that CA significantly inhibited proliferation, invasion, and migration, whereas it induced the apoptosis of NSCLC cells. CA inhibited tumor growth in vivo. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that these differentially expressed mRNAs were potentially implicated in the CA-suppressing malignant phenotypes of NSCLC. According to the competing endogenous RNA (ceRNA) hypothesis, a ceRNA network was constructed, including 13 mRNAs, 6 miRNAs, and 11 lncRNAs. Kyoto Encyclopedia of Genes and Genomes analysis of the 13 mRNAs in the ceRNA network showed that suppressors of cytokine signaling 1 (SOCS1), BTG anti-proliferation factor 2 (BTG2), and Bruton tyrosine kinase (BTK) were significantly enriched in the JAK/STAT signaling pathway, RNA degradation, and nuclear factor-κB (NF-κB) signaling pathway related to cancer. These findings indicated that SOCS1, BTG2, and BTK play an essential role in CA against NSCLC. Meanwhile, based on the ceRNA network, three lncRNAs (long intergenic non-protein coding RNA 1504 [LINC01504], LINC01783, and THUMPD3 antisense RNA 1 [THUMPD3-AS1]) and three miRNAs (has-miR-155-5p, has-miR-7-5p, and has-miR-425-5p) associated with SOCS1, BTG2, and BTK may be important in CA against NSCLC. Taken together, the present study demonstrated the activity of CA against lung cancer and its potential use as a therapeutic agent.
Insights
Cinnamaldehyde (CA) effectively inhibits non-small cell lung cancer (NSCLC) by reducing proliferation and migration while promoting apoptosis. This study identifies key genes and regulatory pathways involved in CA
Area of Science:
- Molecular Oncology
- Cancer Biology
- Pharmacology
Background:
- Cinnamaldehyde (CA), derived from cinnamon, exhibits known antiviral and anti-tumor properties.
- The precise mechanisms of CA's action on non-small cell lung cancer (NSCLC) remain incompletely understood.
- Systematic investigation of CA's effects on NSCLC using transcriptomic analysis is warranted.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying the anti-cancer effects of Cinnamaldehyde (CA) on non-small cell lung cancer (NSCLC).
- To identify key differentially expressed genes and regulatory networks modulated by CA in NSCLC.
- To explore the potential of CA as a therapeutic agent for NSCLC.
Main Methods:
- Whole transcriptome sequencing (RNA sequencing) to identify differentially expressed messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) in NSCLC cells treated with CA.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses to identify enriched biological processes and signaling pathways.
- Construction of a competing endogenous RNA (ceRNA) network to investigate regulatory interactions between lncRNAs, miRNAs, and mRNAs.
Main Results:
- CA significantly inhibited NSCLC cell proliferation, invasion, and migration, while inducing apoptosis.
- CA demonstrated efficacy in inhibiting tumor growth *in vivo*.
- Transcriptomic analysis revealed differentially expressed genes involved in cancer-related pathways, including JAK/STAT and NF-κB signaling.
- A ceRNA network identified key molecules, including SOCS1, BTG2, and BTK, and their associated lncRNAs and miRNAs, as crucial in CA's anti-NSCLC activity.
Conclusions:
- Cinnamaldehyde (CA) exhibits significant anti-cancer activity against non-small cell lung cancer (NSCLC) through multiple molecular mechanisms.
- The identified ceRNA network highlights the roles of SOCS1, BTG2, BTK, specific lncRNAs, and miRNAs in mediating CA's therapeutic effects.
- CA shows promise as a potential therapeutic agent for NSCLC, warranting further clinical investigation.
