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雌激素调节的高迁移率族蛋白A2介导雌激素受体α36促进宫颈癌恶性进展

ER-α36 Promotes the Malignant Progression of Cervical Cancer Mediated by Estrogen HMGA2.

作者信息

Wang Chunyan, Zhang Tianli, Wang Kun, Zhang Shuo, Sun Qing, Yang Xingsheng

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, China.

School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.

出版信息

Front Oncol. 2021 Jul 14;11:712849. doi: 10.3389/fonc.2021.712849. eCollection 2021.

DOI:10.3389/fonc.2021.712849
PMID:34336701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8317436/
Abstract

OBJECTIVES

Estrogen is proven to promote the malignant behaviors of many cancers its receptors. Estrogen receptor alfa 36 (ER-α36) is a newly identified isoform of estrogen receptor alfa (ER-α), the role of ER-α36 in regulating the effects of estrogen and its potential impact on human cervical cancer is poorly understood.

METHODS

Immunohistochemistry staining was used to evaluate the expression of ER-α36, estrogen receptor alfa 66 (ER-α66) and their prognostic values in cervical cancer. The effects of ER-α36 and ER-α66 on the proliferation and metastasis of cervical cancer were measured . A xenograft tumor assay was used to study the tumorigenesis role of ER-α36 . Furthermore, the functional gene at the downstream of ER-α36 was obtained next-generation sequencing, and the biological functions of high mobility group A2 (HMGA2) in cervical cancer cells were investigated .

RESULTS

ER-α36 was over-expressed in cervical cancer tissues and elevated ER-α36 expression was associated with poor prognosis in cervical cancer patients. High expression of ER-α36 promoted the proliferation, invasion and metastasis of cervical cancer cells mediated by estrogen, while silencing ER-α36 had the opposite effects. Further research showed that HMGA2 was a downstream target of ER-α36 in cervical cancer cells. The oncogenic effect of ER-α36 was attenuated after HMGA2 knockdown.

CONCLUSIONS

High expression of ER-α36 was correlated with a poor prognosis in cervical cancer by regulating HMGA2. ER-α36 could be a prognostic biomarker and a target for cervical cancer treatment.

摘要

目的

雌激素被证实可促进多种癌症及其受体的恶性行为。雌激素受体α36（ER-α36）是雌激素受体α（ER-α）新发现的一种亚型，目前对ER-α36在调节雌激素作用中的作用及其对人宫颈癌的潜在影响了解甚少。

方法

采用免疫组织化学染色评估ER-α36、雌激素受体α66（ER-α66）在宫颈癌中的表达及其预后价值。检测ER-α36和ER-α66对宫颈癌增殖和转移的影响。采用异种移植瘤实验研究ER-α36的致瘤作用。此外，通过二代测序获得ER-α36下游的功能基因，并研究高迁移率族蛋白A2（HMGA2）在宫颈癌细胞中的生物学功能。

结果

ER-α36在宫颈癌组织中过表达，ER-α36表达升高与宫颈癌患者预后不良相关。ER-α36的高表达促进雌激素介导的宫颈癌细胞增殖、侵袭和转移，而沉默ER-α36则产生相反的效果。进一步研究表明，HMGA2是宫颈癌细胞中ER-α36的下游靶点。敲低HMGA2后，ER-α36的致癌作用减弱。

结论

ER-α36的高表达通过调节HMGA2与宫颈癌预后不良相关。ER-α36可能是宫颈癌的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/c9b2068d9807/fonc-11-712849-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/b5919fd41af6/fonc-11-712849-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/6e9d1e57b346/fonc-11-712849-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/e3f2f5167220/fonc-11-712849-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/061fc4532f61/fonc-11-712849-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/260e62b0664f/fonc-11-712849-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/282dd08e2c5e/fonc-11-712849-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/415e8a14949d/fonc-11-712849-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/c9b2068d9807/fonc-11-712849-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/b5919fd41af6/fonc-11-712849-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/6e9d1e57b346/fonc-11-712849-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/e3f2f5167220/fonc-11-712849-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/061fc4532f61/fonc-11-712849-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/260e62b0664f/fonc-11-712849-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/282dd08e2c5e/fonc-11-712849-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/415e8a14949d/fonc-11-712849-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5a6/8317436/c9b2068d9807/fonc-11-712849-g008.jpg

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