Sirtuin 6 通过 Hippo 信号通路促进骨髓瘤细胞系 KM-HM_(31)的细胞衰老。

Sirtuin 6 promotes cell aging of myeloma cell line KM-HM_(31) by via Hippo signal pathway.

机构信息

Department of Hematology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Oct;22(20):6880-6884. doi: 10.26355/eurrev_201810_16157.

DOI:10.26355/eurrev_201810_16157

PMID:30402853

Abstract

OBJECTIVE

Myeloma poses a serious risk for people's health and life quality. Molecular targeted treatment of myeloma emerges as a promising therapy. This study aimed to determine the effect of Sirtuin 6 on myeloma KM-HM_(31) cell aging and provide evidence for clinical treatment.

MATERIALS AND METHODS

Myeloma KM-HM_(31) cell aging model induced by Carbamide peroxide (CP) was generated. Cells were transfected with Sirtuin 6 over-expression plasmid and specific siRNA. Western blot was used to study Sirtuin 6 expression, P53, P16, and Hippo in KM-HM_(31) cells. β-galactosidase assay was applied to measure cell aging. Verteporfin inhibited Hippo signal pathway and measured aging of KM-HM_(31) cells.

RESULTS

The levels of Sirtuin 6, aging protein P53, and P16 were remarkably elevated while Hippo expression was significantly inhibited in CP-induced KM-HM_(31) cells. Transfection of Sirtuin 6 over-expression plasmid enhanced Sirtuin 6 expression in KM-HM_(31) cells and potentiated cell aging with downregulation of Hippo protein. In contrast, a block of Sirtuin 6 resulted in the opposite effect. Moreover, Verteporfin inhibited Hippo signal pathway and enhanced CP-induced KM-HM_(31) cell aging, which contributed similar effect as Sirtuin 6 did.

CONCLUSIONS

We showed that sirtuin 6 facilitates CP-induced myeloma cell KM-HM_(31) aging via suppressing Hippo.

摘要

目的

骨髓瘤对人们的健康和生活质量构成严重威胁。骨髓瘤的分子靶向治疗是一种很有前途的治疗方法。本研究旨在探讨 Sirtuin 6 对骨髓瘤 KM-HM_(31)细胞衰老的影响，为临床治疗提供依据。

材料与方法

用过氧化脲（CP）诱导骨髓瘤 KM-HM_(31)细胞衰老模型，转染 Sirtuin 6 过表达质粒和特异性 siRNA，采用 Western blot 检测 KM-HM_(31)细胞中 Sirtuin 6、P53、P16、Hippo 的表达，β-半乳糖苷酶染色检测细胞衰老，应用 Verteporfin 抑制 Hippo 信号通路，检测 KM-HM_(31)细胞衰老。

结果

CP 诱导的 KM-HM_(31)细胞中 Sirtuin 6、衰老蛋白 P53、P16 水平显著升高，Hippo 表达明显抑制。转染 Sirtuin 6 过表达质粒增强了 KM-HM_(31)细胞中 Sirtuin 6 的表达，下调 Hippo 蛋白，促进细胞衰老，而 Sirtuin 6 阻断则产生相反的效果。此外，Verteporfin 抑制 Hippo 信号通路，增强 CP 诱导的 KM-HM_(31)细胞衰老，与 Sirtuin 6 作用相似。