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Let-7a-5p represses proliferation, migration, invasion and epithelial-mesenchymal transition by targeting Smad2 in TGF-β2-induced human lens epithelial cells

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Abstract

Transforming growth factor β2 (TGF-β2)/Smad signaling is widely accepted as a key inducer of proliferation and epithelial-mesenchymal transition (EMT) of human lens epithelial cells (LECs), contributing to the development of posterior capsule opacification (PCO). Increasing evidence shows that microRNAs (miRNAs) play important roles in PCO pathogenesis. Herein, we aimed to explore the role and molecular mechanism of let-7a-5p on TGF-β2-induced proliferation and EMT in LECs. qRT-PCR was performed to detect the expression of let-7a-5p and Smad2 mRNA. Western blot was used to determine the Smad2 level and the induction of EMT. The targeted correlation between let-7a-5p and Smad2 was confirmed using dual-luciferase reporter and RNA immunoprecipitation assays. CCK-8 assay was employed to determine cell proliferation, and transwell assays were performed to assess cell migration and invasion. We found that TGF-β2 induced EMT of LECs, and TGF-β2 upregulated Smad2 expression and reduced let-7a-5p expression in LECs. Smad2 was a direct target of let-7a-5p. Moreover, let-7a-5p upregulation repressed proliferation, migration, invasion and EMT in TGF-β2-induced LECs. But, Smad2 expression restoration abrogated the inhibitory effect of let-7a-5p upregulation. In conclusion, our data indicated that let-7a-5p upregulation repressed TGF-β2-induced proliferation, migration, invasion and EMT at least partly by targeting Smad2 in LECs, highlighting that let-7a-5p might act as a promising therapeutic target to intervene to the progression of PCO.

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Abbreviations

EMT:

epithelial-mesenchymal transition

PCO:

posterior capsule opacification

LECs:

lens epithelial cells

TGF-β2:

transforming growth factor β2

miRNAs:

microRNAs

3′-UTR:

3′-untranslated region

RISC:

RNA-induced silencing complex

Ago:

Argonaute protein

SD:

standard deviation

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Authors and Affiliations

  1. Department of Ophthalmology, The Second Affiliated Hospital of Xi’an Medical University, Xian, Shaanxi, China

    Huifeng Liu

  2. Department of Ophthalmology, Ocular Immunology and Inflammation Institute, Xian, Shaanxi, China

    Huifeng Liu

  3. Department of Ophthalmology, Clinical Research Center of Shaanxi, Xian, Shaanxi, China

    Huifeng Liu

  4. Department of Ophthalmology, The Affiliated Hospital of Zunyi Medical College, Guizhou, China

    Bing Jiang

Authors
  1. Huifeng Liu
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  2. Bing Jiang
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Correspondence to Bing Jiang.

Additional information

Communicated by Sorab Dalal.

Corresponding editor: Sorab Dalal

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Liu, H., Jiang, B. Let-7a-5p represses proliferation, migration, invasion and epithelial-mesenchymal transition by targeting Smad2 in TGF-β2-induced human lens epithelial cells. J Biosci 45, 59 (2020). https://doi.org/10.1007/s12038-020-0001-5

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