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肝脏受体同源物1促进肿瘤细胞增殖和迁移,并与卵巢癌的不良预后相关。

LRH1 Promotes Tumor Cell Proliferation and Migration and Is Correlated With Poor Prognosis in Ovarian Cancer.

作者信息

Sun Wenzhou, Shi Qingtao, Li Jiaxin, Li Jinmeng, Yu Libo

机构信息

Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

Department of Pathology, Harbin Medical University Cancer Hospital, Harbin Medical University, Harbin, China.

出版信息

Front Oncol. 2020 Oct 20;10:583566. doi: 10.3389/fonc.2020.583566. eCollection 2020.

Abstract

BACKGROUND

Liver receptor homolog 1 (LRH1) plays a vital role in several human cancers, but its role in ovarian cancer (OC) remains unclear. We aimed to explore the functions of LRH1 and its clinical relevance.

METHODS

LRH1 expression was evaluated by immunohistochemistry and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The effects of LRH1 on tumor cell proliferation, migration and epithelial-mesenchymal transition (EMT) were evaluated . Furthermore, bioinformatics analysis was applied to predict the functions of LRH1.

RESULTS

RT-qPCR showed that LRH1 mRNA expression was higher in the invasive lesions ( < 0.05). LRH1 overexpression was extremely related with elevated International Federation of Gynecology and Obstetrics (FIGO) stage ( = 0.001), lymph node metastasis ( = 0.011), peritoneal metastasis ( = 0.001), and platinum resistance ( = 0.037). Furthermore, LRH1 expression was an independent prognostic index for disease-free survival in patients with OC ( = 0.041). LRH1 overexpression ( = 0.011), FIGO stage ( < 0.001), and ascites ( = 0.015) independently affected peritoneal metastasis in patients with OC. LRH1 knockdown significantly inhibited the proliferation, migration, and EMT of human OC cells ( < 0.05); however, it reversed cisplatin resistance. Bioinformatics analysis indicated that the functions of LRH1 were associated with the PRC1 complex, nuclear ubiquitin ligase complex, and Polycomb-group (PcG) proteins.

CONCLUSIONS

This study provides evidence of the predictive value of LRH1 on peritoneal metastasis and poor outcome and highlights the potential role of LRH1 as a biomarker for the targeted therapy of OC. Furthermore, LRH1 promotes OC cell proliferation, migration, and EMT , and its functions may be associated with PRC1 complex, nuclear ubiquitin ligase complex, and PcG proteins.

摘要

背景

肝脏受体同源物1(LRH1)在多种人类癌症中发挥着至关重要的作用,但其在卵巢癌(OC)中的作用仍不清楚。我们旨在探讨LRH1的功能及其临床相关性。

方法

通过免疫组织化学和逆转录定量聚合酶链反应(RT-qPCR)评估LRH1的表达。评估LRH1对肿瘤细胞增殖、迁移和上皮-间质转化(EMT)的影响。此外,应用生物信息学分析来预测LRH1的功能。

结果

RT-qPCR显示,LRH1 mRNA在侵袭性病变中的表达较高(<0.05)。LRH1过表达与国际妇产科联盟(FIGO)分期升高(=0.001)、淋巴结转移(=0.011)、腹膜转移(=0.001)和铂耐药(=0.037)密切相关。此外,LRH1表达是OC患者无病生存的独立预后指标(=0.041)。LRH1过表达(=0.011)、FIGO分期(<0.001)和腹水(=0.015)独立影响OC患者的腹膜转移。LRH1敲低显著抑制人OC细胞的增殖、迁移和EMT(<0.05);然而,它逆转了顺铂耐药性。生物信息学分析表明,LRH1的功能与PRC1复合物核泛素连接酶复合物和多梳蛋白组(PcG)蛋白有关。

结论

本研究提供了LRH1对腹膜转移和不良预后的预测价值的证据,并突出了LRH1作为OC靶向治疗生物标志物的潜在作用。此外,LRH1促进OC细胞增殖、迁移和EMT,其功能可能与PRC1复合物、核泛素连接酶复合物和PcG蛋白有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dad2/7641615/e96c85e1ee00/fonc-10-583566-g001.jpg

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