Zhou Liqiang, Chen Zhiqing, Liu Chuan
Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Jiangxi Provincial Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Oncol Lett. 2022 Jun 22;24(2):274. doi: 10.3892/ol.2022.13394. eCollection 2022 Aug.
Studies have shown that methionine restriction (MR) can inhibit tumor progression, but its mechanism in colon cancer is unknown. Through DESeq2 and Edge analysis of the GSE72131 and GSE103602 datasets, 649 co-upregulated and 532 co-downregulated genes affected by MR were identified, respectively. Enrichment analysis showed that these genes were closely associated with tumor progression. Combined with the differentially expressed genes of colon cancer in The Cancer Genome Atlas database, MR affected 330 dysregulated genes in colon cancer. On this basis, a transcriptional regulatory and competing endogenous RNA network was established and F transcription factor 1 and microRNA 17-92a-1 Cluster Host Gene were identified as a key transcription factor and long non-coding RNA, respectively. In addition, four genes (FA Complementation Group I, Holliday Junction Recognition Protein, Karyopherin Subunit Alpha 2 and Kinesin Family Member 15) were identified by analyzing the relationship between dysregulated genes and overall survival. Finally, western blotting, reverse transcription-quantitative PCR, Transwell and other experiments verified that MR inhibits HCT116 colon cancer cell proliferation, metastasis and invasion, induces apoptosis and downregulates 6 hub genes. Collectively, the present study identified potential targets for MR to inhibit colon cancer progression and contributed to the clinical application of MR.
研究表明,蛋氨酸限制(MR)可抑制肿瘤进展,但其在结肠癌中的机制尚不清楚。通过对GSE72131和GSE103602数据集进行DESeq2和Edge分析,分别鉴定出受MR影响的649个共上调基因和532个共下调基因。富集分析表明,这些基因与肿瘤进展密切相关。结合癌症基因组图谱数据库中结肠癌的差异表达基因,MR影响了结肠癌中330个失调基因。在此基础上,建立了转录调控和竞争性内源性RNA网络,并分别将F转录因子1和微小RNA 17-92a-1簇宿主基因鉴定为关键转录因子和长链非编码RNA。此外,通过分析失调基因与总生存期之间的关系,鉴定出四个基因(FA互补组I、霍利迪连接识别蛋白、核转运蛋白亚基α2和驱动蛋白家族成员15)。最后,蛋白质免疫印迹法、逆转录定量PCR、Transwell等实验证实,MR可抑制HCT116结肠癌细胞的增殖、转移和侵袭,诱导细胞凋亡并下调6个枢纽基因。总的来说,本研究确定了MR抑制结肠癌进展的潜在靶点,并为MR的临床应用提供了依据。