ER-alpha 36 Promotes the Malignant Progression of Cervical Cancer Mediated by Estrogen via HMGA2

Objectives Estrogen is proven to promote the malignant behaviors of many cancers via its receptors. Estrogen receptor alfa 36 (ER-alpha 36) is a newly identified isoform of estrogen receptor alfa (ER-alpha), the role of ER-alpha 36 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-alpha 36, estrogen receptor alfa 66 (ER-alpha 66) and their prognostic values in cervical cancer. The effects of ER-alpha 36 and ER-alpha 66 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-alpha 36 in vivo. Furthermore, the functional gene at the downstream of ER-alpha 36 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-alpha 36 was over-expressed in cervical cancer tissues and elevated ER-alpha 36 expression was associated with poor prognosis in cervical cancer patients. High expression of ER-alpha 36 promoted the proliferation, invasion and metastasis of cervical cancer cells mediated by estrogen, while silencing ER-alpha 36 had the opposite effects. Further research showed that HMGA2 was a downstream target of ER-alpha 36 in cervical cancer cells. The oncogenic effect of ER-alpha 36 was attenuated after HMGA2 knockdown. Conclusions High expression of ER-alpha 36 was correlated with a poor prognosis in cervical cancer by regulating HMGA2. ER-alpha 36 could be a prognostic biomarker and a target for cervical cancer treatment.

Automated summary

Estrogen receptor alfa 36 (ER-alpha 36) is over-expressed in cervical cancer tissues and associated with poor prognosis in patients. High expression of ER-alpha 36 promotes proliferation, invasion, and metastasis of cervical cancer cells, with HMGA2 identified as a downstream target. Knockdown of HMGA2 attenuates the oncogenic effects of ER-alpha 36. High expression of ER-alpha 36 may serve as a prognostic biomarker and treatment target in cervical cancer.