NEAT1/miR‑124/STAT3 feedback loop promotes breast cancer progression

Pang,Yamei; Wu,Jie; Li,Xiang; Wang,Cuicui; Wang,Meng; Liu,Jian; Yang,Ganghua

doi:10.3892/ijo.2019.4841

NEAT1/miR‑124/STAT3 feedback loop promotes breast cancer progression

Authors:
- Yamei Pang
- Jie Wu
- Xiang Li
- Cuicui Wang
- Meng Wang
- Jian Liu
- Ganghua Yang
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Affiliations: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Hematology, Zoucheng People's Hospital, Zoucheng, Shandong 273500, P.R. China, Department of Geriatric Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: July 15, 2019 https://doi.org/10.3892/ijo.2019.4841
Pages: 745-754

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Abstract

The long non‑coding RNA nuclear enriched abundant transcript 1 (NEAT1) has important roles in the regulation of multiple cell functions, such as proliferation, apoptosis and migration. However, the mechanism by which NEAT1 regulates breast cancer progression is not well elucidated. In the present study, NEAT1 and microRNA‑124 (miR‑124) levels were detected by reverse transcription‑quantitative PCR in breast cancer tissues and cell lines. STAT3 protein levels were detected by western blot analysis. Cell proliferation and cell cycle distribution were determined using MTT and colony formation assays, and flow cytometry, respectively. The results demonstrated that NEAT1 and STAT3 expression levels were increased in breast cancer tissues compared with normal breast tissues, whereas miR‑124 expression was significantly decreased. Functional analyses revealed that NEAT1 promoted cell proliferation and cell cycle progression in breast cancer cells. Additionally, NEAT1 and STAT3 expression levels were negatively correlated with miR‑124 levels in breast cancer tissues. A direct interaction between miR‑124, and NEAT1 and STAT3, was predicted by bioinformatics analysis and confirmed using a luciferase activity assay. NEAT1 overexpression markedly increased STAT3 protein expression levels, and this effect was reversed by miR‑124 overexpression in breast cancer cells. Furthermore, miR‑124 overexpression partially attenuated the effects of NEAT1 on breast cancer cell proliferation and cell cycle progression. The inhibitory effects of miR‑124 overexpression on the proliferation rate and cell cycle progression were abolished by STAT3 overexpression. In turn, STAT3 silencing inhibited NEAT1 transcription in breast cancer cells. In summary, the present findings revealed that NEAT1 and STAT3 formed a feedback loop via sponging miR‑124 to promote breast cancer progression.

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