RNA Sequencing Analysis of Molecular Basis of Sodium Butyrate-Induced Growth Inhibition on Colorectal Cancer Cell Lines
RNA Sequencing Analysis of Molecular Basis of Sodium Butyrate-Induced Growth Inhibition on Colorectal Cancer Cell Lines
复制标题
丁酸钠诱导结直肠癌细胞系生长抑制的分子基础的 RNA 测序分析
DOI：
10.1155/2019/1427871
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发表时间：
2019-02
影响因子：
--
通讯作者：
Xiaoqin Yuan
中科院分区：
文献类型：
--
作者：
Qianwen Zhou;Guiqin Li;Siyu Zuo;Wenjing Zhu;Xiaoqin Yuan
丁酸盐是从膳食纤维中分解的短链脂肪酸，并且已被证明具有抑制结肠直肠癌细胞增殖但诱导细胞凋亡的作用。然而，临床试验产生了模糊的结果，其抗肿瘤活性。本研究旨在探讨大肠癌细胞对丁酸钠（NaB）敏感性的分子机制。RNA测序用于在NaB处理的结肠直肠癌细胞与未处理的结肠直肠癌细胞中建立全转录组谱。差异表达的基因进行了生物信息学分析，以预测他们可能参与NaB触发的细胞死亡，并通过定量实时PCR验证了8个失调基因的表达。我们发现，与未处理的对照相比，NaB处理的细胞中总共有7192个基因（5720个上调，1472个下调，上调或下调的倍数变化≥ 2或≤ 0.5，q值< 0.05）差异表达。Gene Ontology和京都基因百科全书和基因组通路分析表明，差异表达基因富集在DNA复制、细胞周期、同源重组、嘧啶代谢、错配修复等信号通路中，可能参与了NaB诱导的细胞死亡。在已鉴定的因子中，MCM 2 -7复合物可能是NaB的靶点。我们的研究结果为进一步研究可能调控结直肠癌细胞对NaB敏感性的复杂网络提供了重要基础。
Butyrate is a short-chain fatty acid decomposed from dietary fiber and has been shown to have effects on inhibition of proliferation but induction of apoptosis in colorectal cancer cells. However, clinical trials have yielded ambiguous outcomes with regard to its antitumor activities. In this study, we aimed to explore the molecular mechanisms underlying the sensitivity of colorectal cancer cells to sodium butyrate (NaB). RNA sequencing was used to establish the whole-transcriptome profile in NaB-treated versus untreated colorectal cancer cells. Differentially expressed genes were bioinformatically analyzed to predict their possible involvement in NaB-triggered cell death, and the expression of eight dysregulated genes was validated by quantitative real-time PCR. We found that there were a total of 7192 genes (5720 upregulated and 1472 downregulated, fold-change ≥ 2 or ≤ 0.5 for upregulation or downregulation, q-value < 0.05) differentially expressed in NaB-treated cells as compared with the untreated controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated that the differentially expressed genes were enriched in DNA replication, cell cycle, homologous recombination, pyrimidine metabolism, mismatch repair, and other signaling pathways and may take part in NaB-induced cell death. Among the identified factors, the MCM2-7 complex might be a target of NaB. Our findings provide an important basis for further studies of the complicate network that might regulate sensitivity of colorectal cancer cells to NaB.
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DOI：
10.1891/9780826121646.0002
发表时间：
2018-09
期刊：
Cancer Rehabilitation
影响因子：
--
作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
通讯作者：
K. Miller;R. Siegel;R. Khan;A. Jemal
影响因子：
3.1
作者：
Garborg, Kjetil
通讯作者：
Garborg, Kjetil
组蛋白脱乙酰基酶抑制剂在癌症治疗中。
影响因子：
3.4
作者：
Lee MJ;Kim YS;Kummar S;Giaccone G;Trepel JB
通讯作者：
Trepel JB
影响因子：
9.6
作者：
R. Steele
通讯作者：
R. Steele
影响因子：
4.7
作者：
Nelson, R. Scott;Thorson, Alan G.
通讯作者：
Thorson, Alan G.