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miR-125a-3p regulates apoptosis by suppressing TMBIM4 in lens epithelial cells

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Abstract

Purpose

To explore the regulatory effect of miR-125a-3p on lens epithelial cells (LECs) under ultraviolet radiation B (UVB) irradiation.

Methods

The expression of miR-125a-3p in age-related cataract (ARC) specimens and cell models was detected by qRT-PCR. UVB was utilized to establish DNA damage model of LECs. Cell count kit-8 was applied in detecting cell viability. Cell apoptosis ratio was analyzed by flow cytometry. Dual luciferase reports were applied to analyze the mechanism between miRNA and target genes. Nanoparticle tracking analysis, and Western blot were used to identify whether the exosomes were typical exosomes.

Results

miR-125a-3p was upregulated in ARC tissues and LECs treated with UVB. Knockdown of miR-125a-3p in LECs significantly decreased apoptosis and increased viability of UVB-irradiated LECs. We predicted that miR-125a-3p could regulate transmembrane Bax inhibitor motif containing 4 (TMBIM4) by the bioinformatics databases TargetScan, miRBase, and miRWalk. Luciferase reporter assays demonstrated that miR-125a-3p may suppress TMBIM4 protein translation by binding to 3′UTR of TMBIM4 mRNA. Overexpression of miR-125a-3p decreased TMBIM4, which suggested that miR-125a-3p could inhibit TMBIM4. Moreover, knockdown of TMBIM4 decreased cell viability and enhanced cell apoptosis during UVB irradiation. In addition, the exosome secretion of LECs irradiated by UVB was enhanced, and the expression of miR-125a-3p was high. Cell viability was significantly decreased, and cell apoptosis was increased during UVB-exos treatment.

Conclusion

This study indicated that miR-125a-3p regulated apoptosis by suppressing TMBIM4 in LECs under oxidative damage, providing a new idea for clinical therapeutic target of cataract.

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Data availability

Data are available upon reasonable request.

Abbreviations

LECs:

Lens epithelial cells

UVB:

Ultraviolet radiation B

ARC:

Age-related cataract

TMBIM4:

Transmembrane Bax inhibitor motif containing 4

MVBs:

Multivesicular bodies

STR:

Short tandem repeat

DMEM:

Dulbecco’s modified Eagle medium

PBS:

Phosphate-buffered saline

SBI:

Exosome-depleted FBS

NC-exos:

Exosomes derived from normal conditions

UVB-exos:

Exosomes derived from UVB-treated conditions

PI:

Propidium iodide

Si-NC:

small interfering RNA negative control

NC-mimic:

Negative control mimic

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Funding

This study was supported by the National Science Foundation of China (82101101, 82171038 and 81974129), the Postdoctoral Science Foundation of China (2020M671562), the Postdoctoral Science Foundation of Jiangsu Province (2020Z318), the Science and Technology Project of Nantong Municipality (JCZ19088, Nantong, Jiangsu, China).

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Authors and Affiliations

  1. Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu Province, China

    Lihua Kang, Jiawei Luo, Pengfei Li, Guowei Zhang, Miao Wei, Min Ji & Huaijin Guan

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  1. Lihua Kang
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  2. Jiawei Luo
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  3. Pengfei Li
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  4. Guowei Zhang
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  7. Huaijin Guan
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Contributions

LK, JL, PL: substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. LK, GZ: drafting the article. HG: final approval of the version to be published. LK, JL, PL, GZ, MW, MJ, and HG: agreement to be accountable for all aspects of the work including questions related to the accuracy.

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Correspondence to Huaijin Guan.

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All patients signed an informed consent form before collecting specimens. This study was approved by.

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Kang, L., Luo, J., Li, P. et al. miR-125a-3p regulates apoptosis by suppressing TMBIM4 in lens epithelial cells. Int Ophthalmol 43, 1261–1274 (2023). https://doi.org/10.1007/s10792-022-02524-x

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