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Long non-coding RNA TTC28-AS1 attenuates high glucose-induced damage in HK-2 cells depending on the regulation of miR-320a/CD2AP axis

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Abstract

Background

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play crucial roles in DN pathogenesis.

Objective

The purpose of the present study was to explore the role and mechanism of lncRNA tetratricopeptide repeat domain 2B antisense RNA 1 (TTC28-AS1) in DN.

Methods

Cell viability and apoptosis were assessed by the Cell Counting-8 Kit (CCK-8) assay and flow cytometry, respectively. The levels of TTC28-AS1, miR-320a and CD2-associated protein (CD2AP) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. The levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-8 were gauged by enzyme-linked immunosorbent assay (ELISA). Targeted relationship between miR-320a and TTC28-AS1 or CD2AP was evaluated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.

Results

Our data indicated that high glucose (HG) induced HK-2 cell damage by the repression of cell viability and autophagy and the enhancement of cell apoptosis, fibrosis and pro-inflammatory cytokines production. TTC28-AS1 was down-regulated and miR-320a was up-regulated in HG-induced HK-2 cells. TTC28-AS1 overexpression or miR-320a knockdown alleviated HG-induced damage in HK-2 cells. MiR-320 was a molecular mediator of TTC28-AS1 in regulating HG-induced HK-2 cell damage. Moreover, TTC28-AS1 functioned as a post-transcriptional regulator of CD2AP expression by miR-320a. MiR-320a knockdown relieved HG-induced damage in HK-2 cells by up-regulating CD2AP.

Conclusions

Our findings suggest that TTC28-AS1 attenuates HG-induced damage in HK-2 cells at least partially by targeting the miR-320a/CD2AP axis, highlighting its role as a promising therapeutic approach for DN treatment.

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Acknowledgements

Not applicable.

Funding

This study was supported by Xiangyang Science and Technology Projects ([2012] NO.40).

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Author notes

  1. Ji Zhang and Juan Ding contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Xiangyang Central Hospital, Affiliated Hospital of HuBei University of Arts and Science, Xiangyang, Hubei, China

    Ji Zhang

  2. Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of HuBei University of Arts and Science, Xiangyang, Hubei, China

    Juan Ding, Fang Li, Xue Zhou & Hongxia Shuai

  3. Department of General Practice, Xiangyang Central Hospital, Affiliated Hospital of HuBei University of Arts and Science, Xiangyang, Hubei, China

    Ming Yu

Authors
  1. Ji Zhang
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  2. Juan Ding
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  3. Ming Yu
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  4. Fang Li
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  5. Xue Zhou
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  6. Hongxia Shuai
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Contributions

Conceptualization: JZ and JD. Acquisition of data: MY, FL and XZ. Writing and review of manuscript: All authors. Study supervision: HS. Manuscript approval: All authors.

Corresponding author

Correspondence to Hongxia Shuai.

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Ji Zhang, Juan Ding, Ming Yu, Fang Li, Xue Zhou and Hongxia Shuai declare that they have no conflict of interest.

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Zhang, J., Ding, J., Yu, M. et al. Long non-coding RNA TTC28-AS1 attenuates high glucose-induced damage in HK-2 cells depending on the regulation of miR-320a/CD2AP axis. Genes Genom 43, 1471–1482 (2021). https://doi.org/10.1007/s13258-021-01167-z

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