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FUNDC1的高表达预示着预后不良,是改善宫颈癌患者放化疗效果的一个有前景的靶点。

High expression of FUNDC1 predicts poor prognostic outcomes and is a promising target to improve chemoradiotherapy effects in patients with cervical cancer.

作者信息

Hou Hailing, Er Puchun, Cheng Jingjing, Chen Xiuli, Ding Xiaofeng, Wang Yuwen, Chen Xi, Yuan Zhiyong, Pang Qingsong, Wang Ping, Qian Dong

机构信息

Key Laboratory of Cancer Prevention and Therapy, Department of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

出版信息

Cancer Med. 2017 Aug;6(8):1871-1881. doi: 10.1002/cam4.1112. Epub 2017 Jul 18.

Abstract

FUN14 domain containing 1 (FUNDC1) is an important molecule in receptor-dependent mitophagy. However, the roles of FUNDC1 in human cancer biology remain unknown. The aim of this study was to explore the expression and roles of FUNDC1 in cervical cancer. Immunohistochemistry and Western blotting were applied to detect the expression of FUNDC1, and small-hairpin RNA was applied to inhibit the expression of endogenous FUNDC1 in cervical cancer cells. MTT assays and Flow cytometric analysis were applied to examine cell proliferation and apoptosis. Immunofluorescence was used to detect the formation of γH2AX foci and evaluate the extent of DNA damage. Compared with corresponding adjacent noncancerous cervical tissues, the expression of FUNDC1 in cervical cancer cells was significantly increased. High expression of FUNDC1 and the prognosis of patients with cervical cancer were correlated negatively, which could be used as an independent prognostic factor for overall survival and disease-free survival. Depletion of FUNDC1 significantly inhibited the proliferation of tumor cells, induced apoptosis, and enhanced cell sensitivity to cisplatin and ionizing radiation (IR). Our data suggested that FUNDC1 can be used as a prognostic biomarker in patients with cervical cancer, and may be a new therapeutic target to improve the antitumor effects of chemoradiotherapy.

摘要

含FUN14结构域蛋白1(FUNDC1)是受体依赖性线粒体自噬中的一个重要分子。然而,FUNDC1在人类癌症生物学中的作用尚不清楚。本研究旨在探讨FUNDC1在宫颈癌中的表达及作用。采用免疫组织化学和蛋白质印迹法检测FUNDC1的表达,并运用小发夹RNA抑制宫颈癌细胞中内源性FUNDC1的表达。采用MTT法和流式细胞术分析检测细胞增殖和凋亡情况。利用免疫荧光检测γH2AX灶的形成并评估DNA损伤程度。与相应的癌旁非癌宫颈组织相比,宫颈癌细胞中FUNDC1的表达显著增加。FUNDC1的高表达与宫颈癌患者的预后呈负相关,可作为总生存和无病生存的独立预后因素。FUNDC1的缺失显著抑制肿瘤细胞增殖,诱导细胞凋亡,并增强细胞对顺铂和电离辐射(IR)的敏感性。我们的数据表明,FUNDC1可作为宫颈癌患者的预后生物标志物,可能是提高放化疗抗肿瘤效果的新治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3fc8/5548885/7339a6d7c0f5/CAM4-6-1871-g001.jpg

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