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陈佳乐, 帕尔哈提·沙依木, 舒垠, 苏比依努尔·苏拉依曼, 艾克热木·玉苏甫. TFF3依赖TWIST1上调TRIB3促结直肠癌转移的机制[J]. 肿瘤防治研究, 2024, 51(2): 85-90. DOI: 10.3971/j.issn.1000-8578.2024.23.0906
引用本文: 陈佳乐, 帕尔哈提·沙依木, 舒垠, 苏比依努尔·苏拉依曼, 艾克热木·玉苏甫. TFF3依赖TWIST1上调TRIB3促结直肠癌转移的机制[J]. 肿瘤防治研究, 2024, 51(2): 85-90. DOI: 10.3971/j.issn.1000-8578.2024.23.0906
CHEN Jiale, PAERHATI·Shayimu, SHU Yin, SUBIYINUER·Sulayiman, AIKEREMU·Yusufu. Mechanism of TFF3-dependent TWIST1 Upregulating TRIB3 to Promote Colorectal Cancer Metastasis[J]. Cancer Research on Prevention and Treatment, 2024, 51(2): 85-90. DOI: 10.3971/j.issn.1000-8578.2024.23.0906
Citation: CHEN Jiale, PAERHATI·Shayimu, SHU Yin, SUBIYINUER·Sulayiman, AIKEREMU·Yusufu. Mechanism of TFF3-dependent TWIST1 Upregulating TRIB3 to Promote Colorectal Cancer Metastasis[J]. Cancer Research on Prevention and Treatment, 2024, 51(2): 85-90. DOI: 10.3971/j.issn.1000-8578.2024.23.0906

TFF3依赖TWIST1上调TRIB3促结直肠癌转移的机制

Mechanism of TFF3-dependent TWIST1 Upregulating TRIB3 to Promote Colorectal Cancer Metastasis

  • 摘要:
    目的 探讨TFF3基因过表达对结直肠癌HT29细胞增殖、迁移和侵袭能力的影响,以及与癌转移相关的机制。
    方法 构建TFF3过表达的HT29细胞系,qRT-PCR和Western blot法检测TFF3、TWIST1/TRIB3信号通路及上皮间质转化过程中相关mRNA和蛋白的表达,CCK-8法检测HT29细胞增殖能力,细胞划痕实验和Transwell实验评估细胞迁移和侵袭能力,透射电子显微镜观察TFF3过表达前后细胞形态的变化。
    结果 pIRES2-TFF3质粒转染HT29细胞后,相较于对照组,TFF3 mRNA和蛋白表达水平显著升高(P<0.01),细胞增殖、迁移和侵袭能力显著增强(P<0.01),且TWIST1、TRIB3、Vimentin、Snail的表达也显著上升,而E-cadherin的表达则明显下降(P<0.05)。TFF3过表达后的HT29细胞出现了多种变化,如细胞间连接减少、绒毛脱落、伪足形成,以及形态上梭形细胞增多等。
    结论 TFF3过表达可能通过Twist1/TRIB3信号通路促进结直肠癌细胞的EMT过程,从而提高其转移潜力,加速癌症的恶性进展。

     

    Abstract:
    Objective To investigate the effects of TFF3 overexpression on the proliferation, migration, and invasion ability of colorectal cancer HT29 cells and the mechanisms involved in cancer metastasis.
    Methods HT29 cells were transfected with pIRES2-TFF3, and the expression levels of mRNAs and proteins related to TFF3 gene, TWIST1/TRIB3 signaling pathway, and epithelial-mesenchymal transition (EMT) were detected by qRT-PCR and Western blot. The proliferation, migration, and invasion ability of HT29 cells were detected by the CCK-8, cell scratch, and Transwell assays. Changes in cell morphology after TFF3 overexpression were observed through transmission electron microscopy.
    Results After the HT29 cells were transfected with pIRES2-TFF3, the expression levels of TFF3 mRNA and protein significantly increased (P<0.01); cell proliferation, migration, and invasion were significantly enhanced (P<0.01); and the expression of related genes, such as TWIST1, TRIB3, Vimentin, and Snail were significantly upregulated. By contrast, the expression of E-cadherin significantly decreased (P<0.05). Various changes in cell morphology were observed after TFF3 overexpression, such as decrease in cell junctions, loss of cilia, formation of pseudopodia, and increase in fusiform cells.
    Conclusion TFF3 overexpression may promote EMT in colorectal cancer cells through the Twist1/TRIB3 signaling pathway, increase their metastatic potential, and accelerate the malignant progression of colorectal cancer.

     

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