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.

Highlights

  • Lung cancer is the most common type of cancer and the leading cause of cancer-related death

  • The annexin V/propidium iodide apoptosis detection kit was obtained from BD Biosciences (Franklin Lake, NJ, United States)

  • The primary antibodies against phospho-nuclear factor-κB (NF-κB) (p-NF-κB) p65, p-JAK, phospho-signal transducer and activator of transcription 3 (p-STAT3), peroxisome proliferator-activated receptor gamma (PPARγ), and β-actin (1:1,000) were purchased from the Cell Signaling Technology Co., Ltd (Danvers, MA, United States)

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Summary

Introduction

Lung cancer is the most common type of cancer and the leading cause of cancer-related death. It is expected that its incidence rate will continue to increase (Chen et al, 2016). 85% of patients with lung cancer have non-small cell lung cancer (NSCLC). Lung adenocarcinoma and lung squamous cell carcinoma are the major types of NSCLC (Molina et al, 2008; Herbst et al, 2018). The development of drugs has greatly improved the therapy of patients with advanced NSCLC, the 5 years survival rates of these patients remain low (Minguet et al, 2016). It is urgent to identify effective drugs for combating the malignant phenotype of lung cancer and elucidate the anti-tumor molecular mechanism

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