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


ABSTRACT:

Objectives

Estrogen is proven to promote the malignant behaviors of many cancers via 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 in vitro. A xenograft tumor assay was used to study the tumorigenesis role of ER-α36 in vivo. Furthermore, the functional gene at the downstream of ER-α36 was obtained via next-generation sequencing, and the biological functions of high mobility group A2 (HMGA2) in cervical cancer cells were investigated in vitro.

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.

SUBMITTER: Wang C 

PROVIDER: S-EPMC8317436 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

ER-α36 Promotes the Malignant Progression of Cervical Cancer Mediated by Estrogen <i>via</i> HMGA2.

Wang Chunyan C   Zhang Tianli T   Wang Kun K   Zhang Shuo S   Sun Qing Q   Yang Xingsheng X  

Frontiers in oncology 20210714


<h4>Objectives</h4>Estrogen is proven to promote the malignant behaviors of many cancers <i>via</i> 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.<h4>Methods</h4>Immunohistochemistry staining was used to evaluate the expression of ER-α36, estrogen receptor alfa 66 (ER-α66) and their prognostic values in  ...[more]

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