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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.

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