Han Zhijun, Liu Lei, Liu Yaxin, Li Shanqing
Department of Thoracic Surgery, Peking Union Medical College Hospital (PUMCH), Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) Beijing, China.
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4774-81. eCollection 2014.
SIRT6 is a member of the NAD(+)-dependent class III deacetylase sirtuin family. Current studies have revealed that SIRT6 plays important roles in the epigenetic regulation of genes expression and contribute to the proliferation, differentiation and apoptosis of cancer cells. However, the biological function of SIRT6 in lung cancer has not been elucidated. The present study showed that the mRNA and protein levels of SIRT6 were decreased in human non-small cell lung cancer (NSCLC) tissues and cell lines. MTT assay showed that overexpression of SIRT6 could inhibit the proliferation in NSCLC cells. In contrast, SIRT6 knockdown using small interfering RNA promoted NSCLC cells proliferation. On the molecular level, we found that SIRT6 inhibited the expression of Twist1 both at the mRNA and protein levels in NSCLC cells. Taken together, these results demonstrated for the first time that SIRT6 suppressed NSCLC cells proliferation via down-regulation of Twist1 expression and might provide novel therapeutic targets in the treatment of lung cancer.
SIRT6是烟酰胺腺嘌呤二核苷酸（NAD⁺）依赖性Ⅲ类脱乙酰酶沉默调节蛋白家族的成员。目前的研究表明，SIRT6在基因表达的表观遗传调控中发挥重要作用，并参与癌细胞的增殖、分化和凋亡。然而，SIRT6在肺癌中的生物学功能尚未阐明。本研究表明，SIRT6的mRNA和蛋白水平在人非小细胞肺癌（NSCLC）组织和细胞系中降低。MTT试验表明，SIRT6的过表达可抑制NSCLC细胞的增殖。相反，使用小干扰RNA敲低SIRT6可促进NSCLC细胞增殖。在分子水平上，我们发现SIRT6在NSCLC细胞中在mRNA和蛋白水平上均抑制Twist1的表达。综上所述，这些结果首次证明SIRT6通过下调Twist1表达抑制NSCLC细胞增殖，并可能为肺癌治疗提供新的治疗靶点。
