| 梅海涛,郝家领,刘 洋,罗青杉,翁俊勇,温玉刚.GJA1在结直肠癌组织中表达及促进侵袭转移的研究[J].,2021,(17):3201-3206 |
| GJA1在结直肠癌组织中表达及促进侵袭转移的研究 |
| Study on the Expression of GJA1 in Colorectal Cancer Tissue and Its Promotion of Invasion and Metastasis |
| 投稿时间：2021-02-02 修订日期：2021-02-25 |
| DOI：10.13241/j.cnki.pmb.2021.17.001 |
| 中文关键词: 结直肠癌 GJA1 转移 预后 |
| 英文关键词: Colorectal cancer GJA1 Metastasis Prognosis |
| 基金项目:国家自然科学基金项目（81972215；82003060） |
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| 中文摘要: |
| 摘要 目的：间隙连接Alpha-1蛋白（Gap Junction Alpha-1，GJA1）是间隙连接中分布最广泛的蛋白，并在多种肿瘤中起促癌作用，但其在结直肠癌发生、发展的作用研究甚少。本实验旨在探究GJA1在结直肠癌组织中的表达情况及其对结直肠癌细胞系侵袭、转移能力的影响，以期为结直肠癌的诊断和预后寻找新的生物标志物。方法：收集92对结直肠癌及其癌旁组织样本，提取组织RNA，利用qRT-PCR检测GJA1相对表达量，并分析GJA1表达与临床病理特征及预后的相关性。在HCT116和HCT8两种结直肠癌细胞系中分别构建GJA1过表达载体和敲减载体，利用qRT-PCR和、Western Blot检测上皮间充质转化（epithelial-mesenchymal transition, EMT）相关蛋白E-Cadherin、N-Cadherin、Vimentin和Snail的表达变化，利用Wound healing和Transwell实验观察其迁移、侵袭能力的变化。结果：相对于癌旁组织，GJA1在结直肠癌组织中显著低表达。并且结直肠癌中低表达的GJA1与肿瘤分化程度、浸润深度、淋巴血管转移相关，低表达GJA1结直肠癌患者显示更差的总体生存率和更低的无病生存率。此外，过表达GJA1后，结直肠癌细胞E-cadherin的表达升高，N-cadherin、Vimentin和Snail的表达降低，划痕愈合减慢，Transwell转移细胞减少；而敲减GJA1后，结直肠癌细胞E-Cadherin的表达降低，N-Cadherin、Vimentin和Snail的表达升高，划痕愈合加快，Transwell转移细胞增多。结论：GJA1在结直肠癌中低表达，其表达降低可通过EMT促进结直肠癌的侵袭、转移并影响病人预后。 |
| 英文摘要: |
| ABSTRACT Objective: The Gap Junction alpha-1 (GJA1) protein is the most extensive protein in the Gap Junction, and it has been found to promote cancer in a variety of tumors, but its effect on colorectal cancer has not been explored. Therefore, This study aims to explore the expression of GJA1 in colorectal cancer tissues and its influence on the invasion and metastasis ability of colorectal cancer cell lines, so as to find new biomarkers for the diagnosis and prognosis of colorectal cancer. Methods: 92 pairs of colorectal cancer and its adjacent tissues were collected from 2013 to 2014, and tissue RNA was extracted. The relative expression level of GJA1 was detected by qRT-PCR, and the correlation between GJA1 expression and clinicopathology and prognosis was analyzed. GJA1 overexpression vector and GJA1-SI were constructed in HCT116 and HCT8 colorectal cancer cell lines, respectively. qRT-PCR and WB were used to detect the expression changes of invasion and metastasis related proteins E-cadherin, N-cadherin, Vimentin and Snail. Transwell and Wound Healing experiments were used to observe the changes of migration and metastasis ability. Results: GJA1 expression was low in colorectal cancer tissues. Low expression of GJA1 in colorectal cancer is associated with tumor staging, differentiation, invasion and metastasis. Low expression of GJA1 in colorectal cancer is associated with worse overall survival and disease-free survival. After the overexpression of GJA1, the expression of E-cadherin in colorectal cancer cells increased, the expression of N-cadherin, Vimentin and Snail decreased, the Transwell metastasis cells decreased, and the Wound Healing slowed down. After GJA1 knockdown, the expression of E-cadherin in colorectal cancer cells decreased, the expression of N-cadherin, Vimentin and Snail increased, the number of Transwell metastases increased, and the Wound Healing was accelerated. Conclusion: GJA1 expression is low in colorectal cancer, and its decreased expression can promote the invasion and metastasis of colorectal cancer by EMT and affect the prognosis of patients. |
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