Department of Anatomy, Shandong University, School of Medicine, Jinan, Shandong 250012, P, R, China.
Cancer Cell Int. 2013 Aug 20;13(1):83. doi: 10.1186/1475-2867-13-83.
The prognosis of oral squamous cell carcinoma is very poor due to local recurrence and metastasis. This study explores the molecular events involved in oral carcinoma with the goal of developing novel therapeutic strategies. The mitotic spindle is a complex mechanical apparatus required for the accurate segregation of sister chromosomes during mitosis. Spindle and kinetochore associated complex subunit 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. In recent years, much attention has been focused on determining how SKA proteins interact with each other, as well as their biological role in cancer cells. However, the precise role of SKA1 in oral carcinoma remains unknown.
In order to investigate the role of SKA1 in oral cancer, we employed lentivirus-mediated shRNA to silence SKA1 expression in the CAL-27 human oral adenosquamous carcinoma cell line.
Depletion of SKA1 in CAL-27 cells significantly decreased cell proliferation, as determined by MTT and colony formation assays. These results strongly demonstrate that reduced SKA1 protein levels may cause inhibition of tumor formation. The shRNA-mediated depletion of SKA1 also led to G2/M phase cell cycle arrest and apoptosis.
This is the first report to show that SKA1 plays an important role in the progression of oral adenosqamous carcinoma. Thus, silencing of SKA1 by RNAi might be a potential therapy for this disease.
由于局部复发和转移,口腔鳞状细胞癌的预后非常差。本研究旨在探索口腔癌相关的分子事件,以期开发新的治疗策略。有丝分裂纺锤体是有丝分裂过程中姐妹染色体准确分离所必需的复杂机械装置。纺锤体和动粒相关复合物亚基 1(SKA1)是动粒外微管结合亚基复合物的一个组成部分,对于染色体的正确分离至关重要。近年来,人们越来越关注确定 SKA 蛋白如何相互作用,以及它们在癌细胞中的生物学作用。然而,SKA1 在口腔癌中的精确作用仍不清楚。
为了研究 SKA1 在口腔癌中的作用,我们采用慢病毒介导的 shRNA 沉默 CAL-27 人口腔腺鳞癌细胞系中的 SKA1 表达。
CAL-27 细胞中 SKA1 的缺失显著降低了 MTT 和集落形成测定法确定的细胞增殖。这些结果强烈表明,SKA1 蛋白水平的降低可能导致肿瘤形成的抑制。SKA1 的 shRNA 介导的耗竭也导致 G2/M 期细胞周期停滞和细胞凋亡。
这是第一项表明 SKA1 在口腔腺鳞癌进展中起重要作用的报告。因此,通过 RNAi 沉默 SKA1 可能是治疗这种疾病的一种潜在疗法。