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MiR-27b-3p exerts tumor suppressor effects in esophageal squamous cell carcinoma by targeting Nrf2

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Abstract

MiR-27b-3p has been reported to function as tumor suppressor in several tumors, including breast cancer and lung cancer. Recently, miR-27b-3p has been identified to be significantly down-regulated in esophageal cancer. However, the clinical significance and biological role of miR-27b-3p in esophageal squamous cell carcinoma (ESCC) still remain unclear. In this study, the expression levels of miR-27b-3p were significantly reduced in ESCC clinical tissues and ESCC cell lines (EC97069 and TE-1). Moreover, down-regulated expression of miR-27b-3p was associated with poor cell differentiation, TNM stage and lymph node metastasis. Specially, overexpression of miR-27b-3p significantly suppressed cell proliferation, migration and invasion in vitro using CCK-8 and transwell assays. Targetscan bioinformatics predictions and luciferase reporter assay confirmed that nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) was a direct target gene of miR-27b-3p. Nrf2 expression was significantly increased in ESCC tissues compared with adjacent tissues. Up-regulated expression of Nrf2 was correlated with TNM stage and lymph node metastasis. Functionally, knockdown of Nrf2 exhibited similar effects to overexpression of miR-27b-3p. Higher expression of ZO-1, E-cadherin and lower expression of N-cadherin, Vimentin and Claudin-1 were observed after miR-27b-3p overexpression of Nrf2 knockdown. Rescue experiments proved that miR-27b-3p suppressed cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) via suppression of Nrf2. Taken together, the newly identified miR-27b-3p/Nrf2 axis might represent a new candidate therapeutic target for ESCC treatment.

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Abbreviations

ESCC:

Esophageal squamous cell carcinoma

Nrf2:

Nuclear factor erythroid 2-related factor 2

EMT:

Epithelial to mesenchymal transition

DMEM:

Dulbecco’s modified eagle’s medium

FBS:

Fetal bovine serum

NC:

Negative control

CCK-8:

Cell counting kit-8

PVDF:

Polyvinylidene fluoride

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Funding

Natural science foundation of xinjiang uygur autonomous region, grant number 2017D01C413

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Author notes

  1. Mei Han, Na Li, Fanzhou Li and Hua Wang contributed equally to this work

Authors and Affiliations

  1. Department of Digestive System, Xinjiang Medical University Affiliated Tumor Hospital, No. 789, Suzhou East Street, Xinshi District, Urumqi, 830000, Xinjiang, China

    Mei Han, Na Li, Fanzhou Li & Lanying Ma

  2. Basic Medical College of Xinjiang Medical University, Urumqi, Xinjiang, China

    Hua Wang

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  1. Mei Han
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  2. Na Li
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  3. Fanzhou Li
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  4. Hua Wang
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Correspondence to Lanying Ma.

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The authors declare that they have no competing interests.

Ethics approval and consent to participate

This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of Xinjiang Medical University Affiliated Tumor Hospital (Xinjiang, China).

Ethical standards

This study was approved by the Committee on the Ethics of Ethics Committee of Xinjiang Medical University Affiliated Tumor Hospital (Approval number: XMU3109). All of the experiments were performed in accordance with the Declaration of Helsinki.

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Han, M., Li, N., Li, F. et al. MiR-27b-3p exerts tumor suppressor effects in esophageal squamous cell carcinoma by targeting Nrf2. Human Cell 33, 641–651 (2020). https://doi.org/10.1007/s13577-020-00329-7

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  • DOI: https://doi.org/10.1007/s13577-020-00329-7

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