Inhibitory effect of sodium butyrate on colorectal cancer cells and construction of the related molecular network

BMC Cancer

Wu Wei¹  Zhang Chun²  Zhou Qing³  Qi Quan⁴  Han Shuwen⁴  Yang Xi⁴  Xu Jiamin⁵  Zhuang Jing⁵ 

[1] Department of Gastroenterology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, 313000, Huzhou, Zhejiang Province, China;Department of Infectious Disease, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, 313000, Huzhou, Zhejiang Province, China;Department of Nursing, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, 313000, Huzhou, Zhejiang Province, China;Department of Oncology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, 313000, Huzhou, Zhejiang Province, China;Graduate School of Nursing, Huzhou university, No. 1 Bachelor Road, 313000, Huzhou, Zhejiang Province, China;

关键词: Sodium butyrate;    colorectal cancer;    molecular network;    apoptosis;    ceRNA;   

DOI  :  10.1186/s12885-021-07845-1

来源: Springer

【 摘 要 】

BackgroundSodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine.PurposeHere, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s).MethodsThe cell counting kit-8 (CCK-8) assay and EdU assay were used to detect cell proliferation ability, flow cytometry was used to investigate the induction of apoptosis and cell cycle progression, and the scratch-wound healing and transwell assays were used to evaluate cell migration and invasion, respectively. The human CRC genome information for tissues and CRC cells treated with NaB obtained from the NCBI GEO database was reannotated and used for differential RNA analysis. Functional and pathway enrichment analyses were performed for differentially expressed lncRNAs and mRNAs. A protein-protein interaction (PPI) network for the hub genes was constructed using the Cytoscape software. Targeted miRNAs were predicted based on the lnCeDB database, and a ceRNA network was constructed using the Cytoscape software. The Kaplan-Meier method was used to analyze patient prognosis using the clinical information and exon-seq data for CRC obtained from the Broad Institute’s GDAC Firehose platform.ResultsNaB decreased the proliferation ability of CRC cells in a dose- and time-dependent manner. The number of apoptotic CRC cells increased with the increase in NaB concentrations, and NaB induced a G1 phase block in CRC cells. Moreover, NaB suppressed the migratory and invasive capabilities of CRC cells. There were 666 differentially expressed mRNAs and 30 differentially expressed lncRNAs involved in the CRC inhibition by NaB. The PPI network and ceRNA network were constructed based on the differentially expressed mRNAs and lncRNAs. Three differentially expressed mRNAs, including HMGA2, LOXL2, and ST7, were significantly correlated with the prognosis of CRC.ConclusionNaB induces the apoptosis and inhibition of CRC cell proliferation, invasion, and metastasis by modulating complex molecular networks. RNA prediction and molecular network construction need to be the focus of further research in this direction.

【 授权许可】

CC BY