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YWHAE作为一种与HE4相互作用的蛋白质，可通过调节PI3K/AKT和MAPK信号通路来影响卵巢癌的恶性行为。

YWHAE as an HE4 interacting protein can influence the malignant behaviour of ovarian cancer by regulating the PI3K/AKT and MAPK pathways.

作者信息

Li Xiao, Wang Caixia, Wang Shuang, Hu Yuexin, Jin Shan, Liu Ouxuan, Gou Rui, Nie Xin, Liu Juanjuan, Lin Bei

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China MedicalUniversity, No. 36, Sanhao Street, Heping District, Shenyang, 110004, People's Republic of China.

出版信息

Cancer Cell Int. 2021 Jun 9;21(1):302. doi: 10.1186/s12935-021-01989-7.

DOI:10.1186/s12935-021-01989-7
PMID:34107979
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8190858/
Abstract

BACKGROUND

Malignant tumours of the female reproductive system threaten the lives and health of women worldwide, with ovarian cancer having the highest mortality rate. Based on previous work, this study analysed the expression and role of YWHAE in ovarian epithelial tumours.

METHODS

The interaction between YWHAE and HE4 was evaluated via immunoprecipitation, western blot analysis, and cellular immunofluorescence. Immunohistochemistry was used to address the relationship between YWHAE expression, clinicopathological parameters, and patient prognosis. Changes in cell invasion, epithelial-mesenchymal transition, migration, proliferation, apoptosis, and cell cycle before and after differential expression of YWHAE were also explored in ovarian cancer cell lines and via in vivo experiments.

RESULTS

YWHAE was found to interact with HE4, and its expression was positively correlated with HE4 expression. Moreover, YWHAE upregulation was associated with advanced stages of ovarian cancer and poor patient prognosis. In addition, YWHAE enhanced invasion, migration, and proliferation, but inhibited the apoptosis of ovarian cancer cells. These biological effects were found to be mediated by the AKT and MAPK signalling pathways.

CONCLUSIONS

Altogether, this study demonstrates that YWHAE is substantially upregulated in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream pathways may represent new therapeutic targets for ovarian cancer.

摘要

背景

女性生殖系统恶性肿瘤威胁着全球女性的生命健康，其中卵巢癌死亡率最高。基于以往的研究工作，本研究分析了YWHAE在卵巢上皮性肿瘤中的表达及作用。

方法

通过免疫沉淀、蛋白质印迹分析和细胞免疫荧光评估YWHAE与HE4之间的相互作用。采用免疫组织化学方法探讨YWHAE表达与临床病理参数及患者预后之间的关系。还在卵巢癌细胞系中及通过体内实验研究了YWHAE差异表达前后细胞侵袭、上皮-间质转化、迁移、增殖、凋亡及细胞周期的变化。

结果

发现YWHAE与HE4相互作用，其表达与HE4表达呈正相关。此外，YWHAE上调与卵巢癌晚期及患者预后不良相关。另外，YWHAE增强了卵巢癌细胞的侵袭、迁移和增殖，但抑制了其凋亡。这些生物学效应被发现是由AKT和MAPK信号通路介导的。

结论

总之，本研究表明YWHAE在卵巢癌组织中显著上调，是卵巢癌预后的一个危险因素，与HE4表达呈正相关。此外，YWHAE及其下游通路可能代表卵巢癌新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/6b0dd604eaea/12935_2021_1989_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/91d6ea089963/12935_2021_1989_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/7444aedde676/12935_2021_1989_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/26404f21f765/12935_2021_1989_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/aca6bea07155/12935_2021_1989_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/275210364ac9/12935_2021_1989_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/4559c8f7cf82/12935_2021_1989_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/5038e462c7a4/12935_2021_1989_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/9f49eb789a7d/12935_2021_1989_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/6b0dd604eaea/12935_2021_1989_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/91d6ea089963/12935_2021_1989_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/7444aedde676/12935_2021_1989_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/26404f21f765/12935_2021_1989_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/aca6bea07155/12935_2021_1989_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/275210364ac9/12935_2021_1989_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/4559c8f7cf82/12935_2021_1989_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/5038e462c7a4/12935_2021_1989_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/9f49eb789a7d/12935_2021_1989_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e97/8190858/6b0dd604eaea/12935_2021_1989_Fig9_HTML.jpg

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