17β‑Estradiol treatment drives Sp1 to upregulate MALAT‑1 expression and epigenetically affects physiological processes in U2OS cells

Hu,Qiongying; Li,Shuiqin; Chen,Changjin; Zhu,Menglin; Chen,Yiming; Zhao,Ziyi

doi:10.3892/mmr.2017.6115

17β‑Estradiol treatment drives Sp1 to upregulate MALAT‑1 expression and epigenetically affects physiological processes in U2OS cells

Authors:
- Qiongying Hu
- Shuiqin Li
- Changjin Chen
- Menglin Zhu
- Yiming Chen
- Ziyi Zhao
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Affiliations: Department of Laboratory Medicine, The Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, Department of Hepatobiliary Surgery, The Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, Central Laboratory, The Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, Chengdu Experimental Foreign Languages School, Chengdu, Sichuan 610000, P.R. China, Chengdu Shude Middle School (Guang Hua), Chengdu, Sichuan 610091, P.R. China
Published online on: January 12, 2017 https://doi.org/10.3892/mmr.2017.6115
Pages: 1335-1342

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Abstract

Osteosarcoma is the most common primary bone tumor characterized by high risk of metastasis, thus presents with an overall survival rate of 60%, despite the use of chemotherapy and surgery. Metastasis‑associated lung adenocarcinoma transcript 1 (MALAT‑1) has been reported to upregulated and epigenetically regulate the metastasis in osteosarcoma; however, the regulatory mechanisms of MALAT‑1 expression remain unclear. In the current study, significant upregulation of MALAT‑1 was observed subsequent to exposure to low concentrations of 17β‑estradiol (E2) in U2OS cells. Using chromatin immunoprecipitation assays, E2‑activated estrogen receptor α (ERα) was identified to promote the binding of specificity protein 1 (Sp1) to the MALAT‑1 promoter. Electrophoretic mobility shift assay and immunoprecipitation results demonstrate that ERα binds indirectly to the MALAT‑1 promoter by binding directly to Sp1 protein. Notably, without E2 stimulation, overexpressed ERα results in no significant promotion of the Sp1/MALAT‑1 promoter, indicating that the translocation of ERα to nuclei stimulated by E2 is necessary. The immunofluorescence assay confirmed that E2 stimulation promotes the translocation of Sp1 to the nuclei in an ERα‑dependent manner. Subsequently, the effects of E2 on osteosarcoma physiological processes were further analyzed. Consistently, E2 treatment was observed to promote proliferation, colony formation, migration and invasion in U2OS cells. Taken together, the results indicate a role for E2 in regulating the physiological processes of osteosarcoma cells by regulating MALAT‑1 expression levels.

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