Hou Zhichao, Abudureheman Abulajiang, Wang Lei, Hasim Ayshamgul, Ainiwaer Julaiti, Zhang Haiping, Niyaz Madiniyat, Upur Halmurat, Sheyhidin Ilyar
Department of Thoracic Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uyghur Autonomous Region, PR China.
Department of Pathology of Medical University of Xinjiang, Urumqi, Xinjiang Uyghur Autonomous Region, PR China.
Oncotarget. 2017 Apr 8;8(36):60539-60557. doi: 10.18632/oncotarget.16966. eCollection 2017 Sep 1.
Thsd7a (Thrombospondin type 1 domain containing 7a) is a critical transmembrane protein. Studies have indicated that Thsd7a was associated with cytoskeletal organization, cell migration and filopodia formation. However, the involvement of Thsd7a remains elusive in human Esophageal Squamous Cell Carcinoma (ESCC). Consequently, immunohistochemistry and reverse transcription-polymerase chain reaction were utilized to study the correlation between the expression of Thsd7a and clinical-pathological characteristics. The influence of Thsd7a on apoptosis, cell proliferating activity, cell cycle, migratory and invasive capacity was determined in Eca 109 and EC 9706 cell lines . And the influence on proliferating activity was testified using naked mice model . In addition, the potential molecular mechanism was tested by microarray. It was discovered that there is a certain correlation between Thsd7a and the Kazakh ESCC. By knocking out Thsd7a, the invasion, migration and proliferation could be decreased. And it could also arrest the cell cycle at G1 phase and increase the apoptosis rate. It was further verified that Thsd7a had obvious effect on proliferation in naked mice with xenograft of Eca109 cells. Finally, it was uncovered by microarray analysis that a variety of tumor genes and pathways related to Thsd7a. Together, it was demonstrated that Thsd7a might have a certain degree of carcinogenesis in ESCC.
Thsd7a（含血小板反应蛋白1结构域7a）是一种关键的跨膜蛋白。研究表明，Thsd7a与细胞骨架组织、细胞迁移和丝状伪足形成有关。然而，Thsd7a在人类食管鳞状细胞癌（ESCC）中的作用仍不清楚。因此，采用免疫组织化学和逆转录-聚合酶链反应来研究Thsd7a表达与临床病理特征之间的相关性。在Eca 109和EC 9706细胞系中测定了Thsd7a对细胞凋亡、细胞增殖活性、细胞周期、迁移和侵袭能力的影响。并使用裸鼠模型验证了对增殖活性的影响。此外，通过基因芯片检测潜在的分子机制。发现Thsd7a与哈萨克族ESCC之间存在一定的相关性。通过敲除Thsd7a，可以降低侵袭、迁移和增殖能力。它还可以将细胞周期阻滞在G1期并提高凋亡率。进一步证实Thsd7a对Eca109细胞异种移植裸鼠的增殖有明显影响。最后，通过基因芯片分析发现了多种与Thsd7a相关的肿瘤基因和通路。总之，证明Thsd7a在ESCC中可能具有一定程度的致癌作用。
