Fu Ming-Sheng, Pan Shu-Xian, Cai Xun-Quan, Lv Cui-Ting, Pan Qin-Cong
Department of Gastroenterology, Shanghai Fifth People's Hospital Fudan University, No. 801, Heqing Road, Minhang District, Shanghai 200240, China.
Department of Anesthesiology, Shanghai Fifth People's Hospital Fudan University, Shanghai 200240, China.
Scientifica (Cairo). 2024 Jun 6;2024:5791613. doi: 10.1155/2024/5791613. eCollection 2024.
The aim of this study is to explore the mechanism by which regulates the proliferation and growth of colon cancer cells, and it relates to the metastasis of colorectal cancer (CRC). Various techniques including western blot, CCK8, qRT-PCR, RNA seq assay, plate cloning, subcutaneous tumorigenesis assays, and bioinformatics tools were employed to identify genes that were upregulated or downregulated upon knockdown and their involvement in tumor cell proliferation and growth. The expression of ARHGAP4 in T and M stages of CRC uses immunohistochemistry. The expression levels of ARHGAP4 were found to be high in SW620, SW480, and HCT116 cell lines, while they were being low in HT29, LoVo, and NCM460 cell lines. Depletion of resulted in inhibited proliferation and growth in SW620 cells and inhibited subcutaneous tumorigenesis in nude mice, whereas overexpression of promoted proliferation and growth in HT29 cells and promoted subcutaneous tumorigenesis in nude mice. A total of 318 upregulated genes and 637 downregulated genes were identified in SW620 cells upon knockdown. The downregulated genes were primarily associated with cell cycle pathways, while the upregulated genes were enriched in differentiation-related pathways. Notable upregulated genes involved in cell differentiation included KRT10, KRT13, KRT16, IVL, and CD24, while significant downregulation was observed in genes related to the cell cycle such as CCNA2, CDKN2C, CDKN3, CENPA, and CENPF. ARHGAP4 expression is markedly elevated in the M1 stage of CRC compared to the M0 stage, suggesting ARHGAP4 linked to the metastatic in CRC. regulates the proliferation and growth of colon cancer cells by up- and downregulated cell cycle and differentiation-related molecules, which may be related to the metastasis of CRC.
本研究旨在探索[具体物质]调节结肠癌细胞增殖和生长的机制，以及其与结直肠癌（CRC）转移的关系。采用了包括蛋白质免疫印迹法、CCK8法、qRT-PCR、RNA测序分析、平板克隆、皮下成瘤实验以及生物信息学工具等多种技术，以鉴定在[具体物质]敲低后上调或下调的基因，以及它们在肿瘤细胞增殖和生长中的作用。采用免疫组织化学法检测CRC患者T期和M期组织中ARHGAP4的表达。发现ARHGAP4在SW620、SW480和HCT116细胞系中表达较高，而在HT29、LoVo和NCM460细胞系中表达较低。[具体物质]的缺失导致SW620细胞增殖和生长受到抑制，并抑制裸鼠皮下成瘤，而[具体物质]的过表达促进HT29细胞增殖和生长，并促进裸鼠皮下成瘤。在[具体物质]敲低后的SW620细胞中，共鉴定出318个上调基因和637个下调基因。下调基因主要与细胞周期途径相关，而上调基因则富集于分化相关途径。参与细胞分化的显著上调基因包括KRT10、KRT13、KRT16、IVL和CD24，而与细胞周期相关的基因如CCNA2、CDKN2C、CDKN3、CENPA和CENPF则显著下调。与M0期相比，CRC的M1期ARHGAP4表达明显升高,提示ARHGAP4与CRC转移有关。[具体物质]通过上调和下调细胞周期及分化相关分子来调节结肠癌细胞的增殖和生长，这可能与CRC的转移有关。
