High expression of FUNDC1 predicts poor prognostic outcomes and is a promising target to improve chemoradiotherapy effects in patients with cervical cancer.
High expression of FUNDC1 predicts poor prognostic outcomes and is a promising target to improve chemoradiotherapy effects in patients with cervical cancer.
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FUNDC1的高表达预示着不良的预后结果，是改善宫颈癌患者放化疗效果的一个有希望的靶点
DOI：
10.1002/cam4.1112
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发表时间：
2017-08
期刊：
影响因子：
4
通讯作者：
Qian D
中科院分区：
文献类型：
--
作者：
Hou H;Er P;Cheng J;Chen X;Ding X;Wang Y;Chen X;Yuan Z;Pang Q;Wang P;Qian D
FUN14 domain containing 1（FUNDC 1）是受体依赖性线粒体自噬中的重要分子。然而，FUNDC 1在人类癌症生物学中的作用仍然未知。本研究旨在探讨FUNDC 1在宫颈癌组织中的表达及其作用。应用免疫组化和Western blotting检测宫颈癌细胞中FUNDC1的表达，并应用小发夹RNA抑制内源性FUNDC1的表达。MTT法和流式细胞仪检测细胞增殖和凋亡。免疫荧光法检测γH2AX灶的形成，并评价DNA损伤程度。FUNDC 1在宫颈癌细胞中的表达明显高于相应癌旁组织。FUNDC 1的高表达与宫颈癌患者的预后呈负相关，可作为总生存期和无病生存期的独立预后因素。FUNDC 1的缺失显著抑制肿瘤细胞的增殖，诱导凋亡，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，FUNDC 1可以作为宫颈癌患者的预后生物标志物，并可能成为一个新的治疗靶点，以提高放化疗的抗肿瘤效果。
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.
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