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    李帅, 刘博文, 樊瑞智, 许腾, 宋军. LMO7通过CUL4A促进结直肠癌转移的机制研究[J]. 徐州医科大学学报, 2023, 43(6): 398-403. DOI: 10.3969/j.issn.2096-3882.2023.06.002
    引用本文: 李帅, 刘博文, 樊瑞智, 许腾, 宋军. LMO7通过CUL4A促进结直肠癌转移的机制研究[J]. 徐州医科大学学报, 2023, 43(6): 398-403. DOI: 10.3969/j.issn.2096-3882.2023.06.002
    LI Shuai, LIU Bowen, FAN Ruizhi, XU Teng, SONG Jun. The mechanism of LMO7 in promoting the metastasis of colorectal cancer via CUL4A[J]. Journal of Xuzhou Medical University, 2023, 43(6): 398-403. DOI: 10.3969/j.issn.2096-3882.2023.06.002
    Citation: LI Shuai, LIU Bowen, FAN Ruizhi, XU Teng, SONG Jun. The mechanism of LMO7 in promoting the metastasis of colorectal cancer via CUL4A[J]. Journal of Xuzhou Medical University, 2023, 43(6): 398-403. DOI: 10.3969/j.issn.2096-3882.2023.06.002

    LMO7通过CUL4A促进结直肠癌转移的机制研究

    The mechanism of LMO7 in promoting the metastasis of colorectal cancer via CUL4A

    • 摘要: 目的 探究LIM结构域蛋白7(LMO7)在结直肠癌中的表达及其调控结直肠癌细胞迁移、侵袭能力的机制。方法 采用qRT-PCR检测正常组织、结直肠癌组织中LMO7的表达情况。采用Transwell实验检测敲低或过表达LMO7对结直肠癌细胞迁移、侵袭能力的影响。采用生物信息学方法预测LMO7的共表达分子。qRT-PCR和Western blot检测过表达或沉默LMO7后CUL4A表达水平的变化。采用染色质免疫沉淀实验(ChIP)探究LMO7结合CUL4A启动子区域促进其表达的机制。结果 与正常组织相比,LMO7在无转移结直肠癌组织、伴转移结直肠癌组织中的表达量依次上调(P<0.05)。与人正常结直肠黏膜细胞株FHC相比,LMO7在5种结直肠癌细胞株中的表达水平明显上调(P<0.05)。敲低LMO7抑制HCT116和SW480细胞的迁移、侵袭能力,过表达LMO7增强HCT116和SW480细胞的迁移、侵袭能力。过表达LMO7会促进CUL4A的表达,而沉默LMO7会抑制CUL4A的表达。LMO7可能通过结合CUL4A启动子P3区域促进其表达。结论 LMO7在结直肠癌组织和细胞中呈高表达,通过结合CUL4A的启动子P3区域增强其表达,促进结直肠癌的迁移和侵袭。

       

      Abstract: Objective To investigate the expression of LIM domain only 7 (LMO7) in colorectal cancer and its mechanism of regulating the migration and invasion of colorectal cancer cells.Methods The levels of LMO7 in normal and colorectal cancer tissues were detected by qRT-PCR. The effect of LMO7 knockdown or overexpression on the migration and invasion of colorectal cancer cells were evaluated by Transwell assay. The co-expressed molecules of LMO7 were predicted by bioinformatic methods. The changes in the expression of CUL4A after LMO7 overexpression or silencing were examined by qRT-PCR and Western blot. The mechanisms by which LMO7 promoted the expression of CUL4A through binding to the promoter region of CUL4A were explored by chromatin immunoprecipitation (ChIP) experiments.Results Compared with normal tissues, the levels of LMO7 were upregulated in non-metastatic and metastatic colon cancer tissues (P<0.05). Compared with human normal colonic mucosal cell line FHC, the levels of LMO7 were significantly upregulated in five colon cancer cell lines (P<0.05). LMO7 knockdown inhibited the migration and invasion of HCT116 and SW480 cells, while overexpression of LMO7 enhanced the migration and invasion of these cells. Overexpression of LMO7 promoted the expression of CUL4A, while LMO7 silencing suppressed the expression of CUL4A. LMO7 might promote the expression of CUL4A through binding to the P3 region of CUL4A promoter.Conclusions LMO7 is highly expressed in colorectal cancer tissue and colorectal cancer cells. It promotes the migration and invasion of colorectal cancer through binding to the P3 region of CUL4A promoter to increase its expression.

       

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