Department of Oncology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, No.1558, Sanhuan North Road, Wuxing District, Huzhou, 313000, Zhejiang Province, China.
Graduate School of Nursing, Huzhou university, No. 1 Bachelor Road, Huzhou, 313000, Zhejiang Province, China.
BMC Cancer. 2021 Feb 6;21(1):127. doi: 10.1186/s12885-021-07845-1.
Sodium butyrate (NaB) is produced through the fermentation of dietary fiber that is not absorbed and digested by the small intestine.
Here, we aimed to investigate the effects of NaB on the proliferation, invasion, and metastasis of CRC cells and their potential underlying molecular mechanism(s).
The 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.
NaB 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.
NaB 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.
丁酸钠（NaB）是通过未被小肠吸收和消化的膳食纤维发酵产生的。
本研究旨在探讨丁酸钠对 CRC 细胞增殖、侵袭和转移的影响及其潜在的分子机制。
使用细胞计数试剂盒-8（CCK-8）和 EdU 检测试剂盒检测细胞增殖能力，流式细胞术检测细胞凋亡和细胞周期进程的诱导，划痕愈合和 Transwell 检测分别用于评估细胞迁移和侵袭。从 NCBI GEO 数据库中重新注释了 NaB 处理的组织和 CRC 细胞的人类 CRC 基因组信息，并进行了差异 RNA 分析。对差异表达的 lncRNA 和 mRNA 进行了功能和通路富集分析。使用 Cytoscape 软件构建了用于 hub 基因的蛋白质-蛋白质相互作用（PPI）网络。基于 lnCeDB 数据库预测了靶向 miRNA，并使用 Cytoscape 软件构建了 ceRNA 网络。使用 Broad Institute 的 GDAC Firehose 平台获得的 CRC 的临床信息和外显子测序数据，采用 Kaplan-Meier 方法分析患者预后。
NaB 呈剂量和时间依赖性地降低 CRC 细胞的增殖能力。随着 NaB 浓度的增加，CRC 细胞的凋亡数量增加，NaB 诱导 CRC 细胞 G1 期阻滞。此外，NaB 抑制 CRC 细胞的迁移和侵袭能力。有 666 个差异表达的 mRNA 和 30 个差异表达的 lncRNA 参与了 NaB 抑制 CRC。基于差异表达的 mRNA 和 lncRNA 构建了 PPI 网络和 ceRNA 网络。三个差异表达的 mRNAs，包括 HMGA2、LOXL2 和 ST7，与 CRC 的预后显著相关。
NaB 通过调节复杂的分子网络诱导 CRC 细胞凋亡和抑制增殖、侵袭和转移。RNA 预测和分子网络构建需要成为该方向进一步研究的重点。
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