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miR-135b-5p Targets SIRT1 to Inhibit Deacetylation of c-JUN and Increase MMP7 Expression to Promote Migration and Invasion of Nasopharyngeal Carcinoma Cells

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Abstract

NPC is a type of cancer with a poor prognosis. We aim to excavate the regulatory roles of miR-135b-5p in NPC and uncover the underlying mechanism. The levels of miR-135b-5p and Sirtuin 1 (SIRT1) in NPC and normal tissues and cells were tested via quantitative real-time PCR, western blotting, and immunohistochemistry, respectively. The binding relationship between them was predicted with ENCORI databases and validated with dual-luciferase reporter assay. The impact of miR-135b-5p and SIRT1 on the expressions of matrix metalloproteinase 7 (MMP7) and epithelial–mesenchymal transformation (EMT) proteins in NPC cells was evaluated by western blotting. Metastasis of NPC cells was evaluated by Transwell assay. The binding of c-JUN at the MMP7 promoter and deacetylation of c-JUN were examined using chromatin-immunoprecipitation and co-immunoprecipitation, respectively. The level of miR-135b-5p was increased and SIRT1 was decreased in NPC tissues and cells. miR-135b-5p was validated to target SIRT1. Silencing of miR-135b-5p accelerated EMT and metastasis of NPC cells, whereas knockdown of SIRT1 showed opposite results. Notably, knockdown of SIRT1 partially reversed the miR-135b-5p-induced change of EMT markers and metastasis of NPC cells. Mechanistically, miR-135b-5p disrupted SIRT1-induced deacetylation of c-JUN to promote the activation of MMP7 in NPC cells. miR-135b-5p targeted SIRT1 to inhibit deacetylation of c-JUN and increase MMP7 expression to promote malignancy of NPC cells.

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Data Availability

The datasets used during the present study are available from the corresponding author upon reasonable request.

Abbreviations

NPC:

Nasopharyngeal carcinoma

qRT-PCR:

Quantitative real-time PCR

miRs/miRNAs:

MicroRNAs

DLR:

Dual-luciferase reporter

IHC:

Immunohistochemistry

EBV:

Epstein-Barr virus

EMT:

Epithelial–mesenchymal transformation

SIRT1:

Sirtuin 1

Sir2:

Silent information regulator 2

MMP7:

Matrix metalloproteinase 7

RFS:

Relapse-free survival

ECM:

Extracellular matrix

ChIP:

Chromatin-immunoprecipitation

Co-IP:

Co-immunoprecipitation

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  1. Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Shandong First Medical University, No. 16766, Jingshi Road, Jinan, 250014, Shandong, China

    Yali Cheng

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YC performed all of the work of this research and gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

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The methodologies of this research were approved by the Ethics Committee of The First Affiliated Hospital of Shandong First Medical University and obeyed the principles of the Declaration of Helsinki.

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Cheng, Y. miR-135b-5p Targets SIRT1 to Inhibit Deacetylation of c-JUN and Increase MMP7 Expression to Promote Migration and Invasion of Nasopharyngeal Carcinoma Cells. Mol Biotechnol 64, 693–701 (2022). https://doi.org/10.1007/s12033-022-00457-5

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