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TGM2 干扰通过 Wnt/β-catenin 通路调节结直肠癌的血管生成和细胞凋亡。

TGM2 interference regulates the angiogenesis and apoptosis of colorectal cancer via Wnt/β-catenin pathway.

机构信息

a Department of Anal-Colorectal Surgery , General Hospital of Ningxia Medical University , Yinchuan , China.

出版信息

Cell Cycle. 2019 May;18(10):1122-1134. doi: 10.1080/15384101.2019.1609831. Epub 2019 May 8.

Abstract

Angiogenesis and apoptosis are critical for the growth of colorectal cancer (CRC). The study aimed to investigate the effects of TGM2 in CRC. Forty-two patients were recruited and their TGM2 levels were detected by performing Realtime-qPCR (RT-qPCR), Western blot and immunohistochemistry , respectively. Levels of TGM2, MMP-2 and MMP-9 in four CRC cell lines and in normal cells were determined using RT-qPCR and Western blot. TGM2-siRNA was transfected into LoVo and HCT116 cells, respectively. TGM2 levels, cell viability, cell apoptosis, angiogenesis and related factors were determined. the tumorigenesis rates of mice were detected after TGM2-siRNA transfection. TGM2 were upregulated in patients with CRC. High TGM2 level of CRC patients had a lower survival rate. The levels of TGM2, MMP-2 and MMP-9 were upregulated in all detected CRC cell lines. Silencing TGM2 could inhibit cell viabilities, angiogenesis and suppress the expressions of MMP-2, MMP-9, Wnt3a, β-catenin and Cyclin D1 , whereas cell apoptosis and the expressions of Caspase-3 and TIMP-1 were promoted. Tumor weights and volumes were reduced by TGM2-siRNA interference. The effects of TGM2-siRNA interference might be related to Wnt/β-catenin Pathway. This might prove that TGM2 could be used as a molecular target in the treatment of CRC.

摘要

血管生成和细胞凋亡对于结直肠癌(CRC)的生长至关重要。本研究旨在探讨 TGM2 在 CRC 中的作用。分别通过 Realtime-qPCR(RT-qPCR)、Western blot 和免疫组织化学检测 42 名患者的 TGM2 水平。使用 RT-qPCR 和 Western blot 检测四种 CRC 细胞系和正常细胞中 TGM2、MMP-2 和 MMP-9 的水平。分别将 TGM2-siRNA 转染到 LoVo 和 HCT116 细胞中,检测 TGM2 水平、细胞活力、细胞凋亡、血管生成和相关因子。转染 TGM2-siRNA 后检测小鼠的肿瘤发生率。CRC 患者的 TGM2 水平上调。CRC 患者 TGM2 水平高的生存率较低。所有检测的 CRC 细胞系中 TGM2、MMP-2 和 MMP-9 的水平均上调。沉默 TGM2 可抑制细胞活力、血管生成,并抑制 MMP-2、MMP-9、Wnt3a、β-catenin 和 Cyclin D1 的表达,而促进细胞凋亡和 Caspase-3 和 TIMP-1 的表达。TGM2-siRNA 干扰可降低肿瘤重量和体积。TGM2-siRNA 干扰的作用可能与 Wnt/β-catenin 通路有关。这可能证明 TGM2 可以作为 CRC 治疗的分子靶点。

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