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热休克蛋白 47 可通过抑制细胞活力和侵袭、促进细胞凋亡来影响喉鳞状细胞癌的预后。

HSP47 is associated with the prognosis of laryngeal squamous cell carcinoma by inhibiting cell viability and invasion and promoting apoptosis.

机构信息

Department of Otolaryngology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.

出版信息

Oncol Rep. 2017 Oct;38(4):2444-2452. doi: 10.3892/or.2017.5893. Epub 2017 Aug 9.

DOI:10.3892/or.2017.5893
PMID:28849239
Abstract

Heat shock protein 47 (HSP47) is a 47 kDa collagen binding protein that has a close relationship with the development and progression of tumours. However, little is known concerning the expression profile of HSP47 in laryngeal squamous cell carcinoma (LSCC) patients and there is still insufficient data concerning the underlying mechanisms. The aim of the present study was to explore the expression of HSP47 in LSCC and provide an overview of its association with tumourigenicity and clinical prognosis. The expression of HSP47 in LSCC and adjacent non-cancerous laryngeal tissues was assessed via western blotting and immunohistochemical studies. The prognostic significance of HSP47 expression was analysed using a Kaplan-Meier survival curve. To investigate the influence of HSP47 on the viability, invasion and apoptosis of a LSCC cell line, we performed an in vitro analysis with plasmid vectors and small interfering RNA (siRNA). Our results showed that HSP47 protein expression in the LSCC tissues was markedly decreased compared to that noted in the adjacent non-cancerous tissues, and low expression of HSP47 was correlated with poor prognosis in LSCC patients. Upregulation of HSP47 via plasmid vectors inhibited the proliferation, reduced the invasive ability, increased the sensitivity to cisplatin chemotherapy, promoted apoptosis, and induced the G1 phase arrest of LSCC cells in vitro. The expression of apoptosis-regulating proteins was also altered when HSP47 was upregulated, involving increased expression of cleaved caspase-7/-8/-9, PARP, and Bax and decreased expression of Bcl-2. Our present data suggest that HSP47 is an important prognostic factor and an attractive therapeutic target in LSCC due to its influence on the biological behaviour of LSCC cells.

摘要

热休克蛋白 47(HSP47)是一种 47kDa 的胶原蛋白结合蛋白,与肿瘤的发生和发展密切相关。然而,目前对于 HSP47 在喉鳞状细胞癌(LSCC)患者中的表达谱知之甚少,其潜在机制的数据仍然不足。本研究旨在探讨 HSP47 在 LSCC 中的表达情况,并概述其与肿瘤发生和临床预后的关系。通过 Western blot 和免疫组织化学研究评估 HSP47 在 LSCC 和相邻非癌性喉组织中的表达。通过 Kaplan-Meier 生存曲线分析 HSP47 表达的预后意义。为了研究 HSP47 对 LSCC 细胞系活力、侵袭和凋亡的影响,我们使用质粒载体和小干扰 RNA(siRNA)进行了体外分析。结果表明,与相邻非癌组织相比,LSCC 组织中 HSP47 蛋白表达明显降低,HSP47 低表达与 LSCC 患者预后不良相关。通过质粒载体上调 HSP47 抑制了增殖,降低了侵袭能力,增加了对顺铂化疗的敏感性,促进了凋亡,并诱导 LSCC 细胞在体外发生 G1 期阻滞。上调 HSP47 还改变了凋亡调节蛋白的表达,涉及 cleaved caspase-7/-8/-9、PARP 和 Bax 的表达增加以及 Bcl-2 的表达减少。本研究数据表明,由于 HSP47 对 LSCC 细胞生物学行为的影响,HSP47 是 LSCC 中的一个重要预后因素和有吸引力的治疗靶点。

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