Folate receptor alpha is associated with cervical carcinogenesis and regulates cervical cancer cells growth by activating ERK1/2/c-Fos/c-Jun
Folate receptor alpha is associated with cervical carcinogenesis and regulates cervical cancer cells growth by activating ERK1/2/c-Fos/c-Jun
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叶酸受体α与宫颈癌发生相关，并通过激活ERK1/2/c-Fos/c-Jun调节宫颈癌细胞的生长
DOI：
10.1016/j.bbrc.2017.08.015
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发表时间：
2017-09-30
影响因子：
3.1
通讯作者：
Wang, Jintao
中科院分区：
文献类型：
--
作者：
Liu, Chunliang;Ding, Ling;Wang, Jintao
叶酸受体α（FR α）在许多上皮恶性肿瘤中过度表达，然而，FR α与宫颈癌之间的关联仍不清楚。本研究旨在探讨FRa对宫颈癌的作用及其对ERK信号通路的调节作用。在本病例对照研究中，FRa、磷酸化ERK 1/2（p-ERK 1/2）、p-c-Fos和p-c-Jun蛋白的中/强表达随着宫颈病变的进展而增加（P < 0.05）。宫颈鳞癌组织中p-ERK 1/2、p-c-Fos、p-c-Jun蛋白的表达与FRa蛋白的表达呈正相关（P < 0.05）。体外实验表明，siRNA下调FRa基因表达可抑制细胞增殖，促进细胞凋亡，使细胞周期阻滞于G 0/G1期，并降低p-ERK 1/2、p-c-Fos和p-c-Jun蛋白的表达。结果表明，FRa与宫颈癌的发生发展有关，并通过磷酸化ERK 1/2、c-Fos和c-Jun等ERK信号通路的关键因子来调节宫颈癌细胞的生长。因此，FRa可能成为宫颈癌早期检测和治疗的有效靶点。(C)2017爱思唯尔公司All rights reserved.
Folate receptor alpha (FR alpha) is over-expressed in numerous epithelial malignancies, however, the association between FRa and cervical cancer remains unclear. The purpose of this study was to explore the effects of FRa on cervical cancer and its regulation of the ERK signaling pathway. In this case-control study, moderate/strong expression of FRa, phosphorylated ERK1/2(p-ERK1/2), p-c-Fos, and p-c-Jun proteins was increased with the progressive severity of cervix lesions (P < 0.05). Moreover, the expression levels of p-ERK1/2, p-c-Fos, and p-c-Jun proteins was positively correlated with those of FRa protein in cervical squamous cell carcinoma (SCC) group (P < 0.05). In vitro experiment indicated down regulation of FRa by siRNA suppressed cell proliferation, promoted cell apoptosis, induced cell cycle arrest at G0/G1 phase, and reduced expression of p-ERK1/2, p-c-Fos, and p-c-Jun proteins. The results suggest that FRa is associated with the progression of cervical cancer and regulates cervical cancer cells growth through phosphorylating ERK1/2, c-Fos, and c-Jun, which are key factors of the ERK signaling pathway. Therefore, FRa may be an effective target for early detection and therapy of cervical cancer. (C) 2017 Elsevier Inc. All rights reserved.