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MiR-1297 and MiR-26a-5p Inhibit Cell Progression of Keratinocytes in Cholesteatoma Depending on the Regulation of BMI1

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Abstract

Cholesteatoma is a pathologically benign but clinically destructive middle ear disease characterized by hyperproliferative keratinocytes. B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) has been reported to be upregulated in cholesteatoma tissues. This study aimed to explore the biological role and underlying mechanisms of BMI1 in the progression of cholesteatoma. The expression levels of microRNA (miR)-1297, miR-26a- 5p, and BMI1 in cholesteatoma tissues and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Functional experiments were performed by CCK-8 assay for cell proliferation viability, 5-ethynyl-2'deoxyuridine (EdU) incorporation assay for DNA biosynthesis, colony formation assay for cloning forming ability analysis, transwell assay and wound healing assay for cell metastasis, flow cytometry for cell cycle distribution and cell apoptosis. The protein expression of apoptosis-associated proteins was investigated by western blot. Dual-luciferase reporter assay was conducted to verify the interaction between miR-1297 or miR-26a-5p and BMI1. BMI1 was highly expressed in cholesteatoma tumor tissues. Functional analyses showed that BMI1 knockdown could inhibit the proliferation, colony formation, migration, invasion, cell cycle progression and promoted the apoptosis of keratinocytes. Mechanically, BMI1 was a target of miR-1297 and miR-26a-5p. Moreover, the rescue experiments presented that BMI1 addition could abolish the suppressive effects of miR-1297 or miR-26a-5p overexpression on cell malignant behaviors in keratinocytes. BMI1 could exert an oncogenic role in the malignant development of cholesteatoma through serving as the targets of miR-1297 and miR-26a-5p, which might provide novel strategies for cholesteatoma treatment.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450002, Henan, China

    Xiaodan Zhu, Fanglei Ye, Shaojuan Hao, Qiuning Yu, Yang Wang, Weihua Lou, Kun Zhao & Hongmin Li

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  1. Xiaodan Zhu
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  2. Fanglei Ye
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  4. Qiuning Yu
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  8. Hongmin Li
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Correspondence to Weihua Lou.

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Zhu, X., Ye, F., Hao, S. et al. MiR-1297 and MiR-26a-5p Inhibit Cell Progression of Keratinocytes in Cholesteatoma Depending on the Regulation of BMI1. Biotechnol Bioproc E 27, 79–88 (2022). https://doi.org/10.1007/s12257-021-0178-y

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  • DOI: https://doi.org/10.1007/s12257-021-0178-y

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