The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, 410081, China.
College of Biology, State Key Laboratory of Chemo/Biosensing and Chemometrics, and Hunan Key Laboratory of Plant Functional Genomics and Developmental Regulation, Hunan University, Changsha, Hunan, 410082, China.
Mol Omics. 2022 Sep 26;18(8):754-764. doi: 10.1039/d2mo00127f.
Butyrate, a short-chain fatty acid, is predominantly produced by the decomposition of dietary fiber in the colon. Recent studies have shown that sodium butyrate (NaB) can inhibit cell proliferation and stimulate cell apoptosis in colorectal cancer (CRC) cells. However, the molecular mechanism behind NaB is still elusive. In this study, we aimed to explore the deeper mechanism of NaB in CRC by establishing a novel model - organoid. Organoids were generated from healthy and cancerous sites of CRC patients. RNA-seq experiments were undertaken using RNA isolated from the CRC organoids treated with NaB. Gene ontology analyses suggested that cell adhesion, cell-cell signaling, and extracellular matrix (ECM) organization were significantly enriched, with the manifested ECM related to the cell morphology variation in NaB-induced CRC organoids. The KEGG pathway and PPI analysis mainly focused on ECM-receptor interactions, as well as the PI3K-Akt signaling pathway. Interestingly, further analysis suggested that the upregulation of the expression of and was significantly associated with death by NaB-induced CRC organoids. In addition, NaB might further induce cell cycle arrest the PI3K-Akt pathway, and thus cause cell death. Cumulatively, these results provide evidence that the ECM-integrin/PI3K axis may mediate phenotypic changes in the NaB-treated CRC organoid, which provides a broader perspective of the treatment and prognosis monitoring of CRC.
丁酸是一种短链脂肪酸，主要由结肠中膳食纤维的分解产生。最近的研究表明，丁酸钠（NaB）可以抑制结直肠癌细胞（CRC）的增殖并刺激细胞凋亡。然而，NaB 的分子机制仍不清楚。在这项研究中，我们旨在通过建立一种新型的类器官模型来探索 NaB 在 CRC 中的更深层次机制。类器官是从 CRC 患者的健康和癌变部位生成的。使用 NaB 处理的 CRC 类器官中分离的 RNA 进行 RNA-seq 实验。GO 分析表明，细胞黏附、细胞间信号和细胞外基质（ECM）组织显著富集，而 NaB 诱导的 CRC 类器官中表现出的与细胞形态变化相关的 ECM。KEGG 通路和 PPI 分析主要集中在 ECM-受体相互作用以及 PI3K-Akt 信号通路。有趣的是，进一步的分析表明，和 的表达上调与 NaB 诱导的 CRC 类器官的死亡显著相关。此外，NaB 可能通过 PI3K-Akt 通路进一步诱导细胞周期停滞，从而导致细胞死亡。综上所述，这些结果为 ECM-整合素/PI3K 轴可能介导 NaB 处理的 CRC 类器官表型变化提供了证据，为 CRC 的治疗和预后监测提供了更广阔的视角。
