Qin Xihu, Yuan Bo, Xu Xintao, Huang Hai, Liu Yong
Department of Hepatobiliary Surgery, Changzhou Hospital of Traditional Chinese Medicine , Changzhou , China.
Scand J Gastroenterol. 2013 Nov;48(11):1324-32. doi: 10.3109/00365521.2013.828774. Epub 2013 Sep 9.
Hepatocellular carcinoma (HCC) is one of the common causes of cancer resulting in death in China. Here, we found that spindle- and kinetochore-associated complex subunit 1 (SKA1) is a critical factor that plays an essential role in the regulation of HCC cell proliferation and apoptosis.
Using immunohistochemistry in 38 HCC tissues, we showed that the expression of SKA1 was upregulated in HCC tissues compared with the normal tissues. Then, we investigated the effects of SKA1-targeted small interfering RNA (siRNA) on the HCC cell proliferation and apoptosis as of HCC cells. SKA1-targeted siRNA was delivered to HCC SMMC-7721 and Bel-7404 cells to evaluate its antiproliferation effects using lentivirus.
The lentivirus-mediated siRNA-targeting SKA1 treatment leads to a significant (p < 0.01) downregulation of SKA1 expression at mitochondrial RNA (mRNA) level. Knockdown of SKA1 inhibited HCC cell proliferation by inducing cell cycle arrest in the G0/G1 phase. Furthermore, lentivirus-mediated siRNA efficiently inhibited cell proliferation and colony formation while promoting the apoptosis.
Of note, our data suggest that SKA1 might play an important role in the proliferation of HCC cells, and the absence of this gene in HCC may open promising therapeutic approaches for HCC.
肝细胞癌(HCC)是中国导致癌症死亡的常见原因之一。在此,我们发现纺锤体和动粒相关复合体亚基1(SKA1)是在HCC细胞增殖和凋亡调控中起关键作用的一个重要因素。
通过对38例HCC组织进行免疫组化,我们发现与正常组织相比,HCC组织中SKA1的表达上调。然后,我们研究了靶向SKA1的小干扰RNA(siRNA)对HCC细胞增殖和凋亡的影响。将靶向SKA1的siRNA通过慢病毒导入HCC SMMC - 7721和Bel - 7404细胞,以评估其抗增殖作用。
慢病毒介导的靶向SKA1的siRNA处理导致线粒体RNA(mRNA)水平上SKA1表达显著下调(p < 0.01)。敲低SKA1通过诱导细胞周期停滞在G0/G1期抑制HCC细胞增殖。此外,慢病毒介导的siRNA有效抑制细胞增殖和集落形成,同时促进细胞凋亡。
值得注意的是,我们的数据表明SKA1可能在HCC细胞增殖中起重要作用,HCC中该基因的缺失可能为HCC开辟有前景的治疗方法。