Functional role of SIRT1-induced HMGB1 expression and acetylation in migration, invasion and angiogenesis of ovarian cancer
Functional role of SIRT1-induced HMGB1 expression and acetylation in migration, invasion and angiogenesis of ovarian cancer
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DOI：
10.26355/eurrev_201807_15494
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发表时间：
2018-07-01
影响因子：
3.3
通讯作者：
Liu, D-F
中科院分区：
文献类型：
--
作者：
Jiang, W.;Jiang, P.;Liu, D-F
目的：卵巢癌是女性常见的肿瘤。高迁移率族蛋白-1(HHMB1)是一种具有多种功能的染色体相关蛋白。最近的一项研究揭示了HMGB1在卵巢癌的发生和发展中的关键作用。Sirtuin 1(SIRT1)是新近发现的一种调节HMGB1乙酰化的新分子。SIRT1是否参与卵巢癌的迁移、侵袭或血管生成尚不清楚。本研究旨在探讨SIRT1诱导的HMGB1乙酰化在卵巢癌迁移、侵袭和血管生成中的作用。Western印迹和免疫荧光检测HMGB1的表达、乙酰化水平和核转位。采用划痕试验法和Transwell小室法检测细胞的迁移和侵袭能力。建立小鼠卵巢癌细胞移植模型，检测诱导型一氧化氮合酶(INOS)和CD105的表达。结果：与癌旁组织相比，卵巢癌组织中SIRT1的表达明显降低。在卵巢癌细胞中，SIRT1过表达降低HMGB1和乙酰化水平，SIRT1基因敲除促进HMGB1表达和乙酰化。SIRT1过表达也抑制HMGB1的核转位。同时，SIRT1可通过HMGB1抑制卵巢癌细胞的迁移和血管生成。结论：SIRT1过表达可有效抑制HMGB1的表达和乙酰化，从而抑制卵巢癌细胞的迁移、侵袭和血管生成。HMGB1通过SIRT1调控卵巢癌的行为。因此，SIRT1可能成为控制卵巢癌转移的治疗靶点。
OBJECTIVE: Ovarian cancer is a commonly occurred tumor in females. High motility group box-1 protein (HHMB1) is a chromosome-related protein with multiple functions. A recent study revealed critical roles of HMGB1 in occurrence and progression of ovarian cancer. Sirtuin 1 (SIRT1) is a recently identified novel molecule, which regulates acetylation of HMGB1. Whether SIRT1 is involved in migration, invasion or angiogenesis of ovarian cancer is unclear. This study aims to investigate the role of SIRT1-induced HMGB1 acetylation in migration, invasion, and angiogenesis in ovarian cancer.PATIENTS AND METHODS: In ovarian cancer cell line, SIRT1 expression was potentiated. Western blot and immunofluorescence were used to measure HMGB1 expression, acetylation level, and nuclear translocation. Scratch assay and transwell chamber methods were used to examine cell migration and invasion potency. A mouse model with ovarian cancer cell transplantation was generated to measure induced nitric oxide synthase (iNOs) and CD105 expression.RESULTS: Compared to adjacent tissues, ovarian cancer tissues had significantly decreased SIRT1 expression. In ovarian cancer cells, SIRT1 over-expression decreased HMGB1 and acetylation levels, and SIRT1 knockdown facilitated HMGB1 expression and acetylation. SIRT1 over-expression also suppressed nuclear translocation of HMGB1. Meanwhile, SIRT1 could suppress, migration and angiogenesis of ovarian cancer cells via HMGB1.CONCLUSIONS: SIRT1 over-expression effectively inhibited HMGB1 expression and acetylation, thus inhibiting ovarian cancer migration, invasion and angiogenesis. HMGB1 modulated behaviors of ovarian cancer via SIRT1. Therefore, SIRT1 might work as a treatment target for managing ovarian cancer migration.