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

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.

• Authors: Ji Zhang, Juan Ding, Ming Yu, Fang Li, Xue Zhou, Hongxia Shuai
• Journal: Genes & genomics (Genes Genomics) Vol. 43 Issue 12 Pg. 1471-1482 (12 2021) ISSN: 2092-9293 [Electronic] Korea (South)
• PMID: 34623609 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Genetics Society of Korea.

Chemical References

• Adaptor Proteins, Signal Transducing
• CD2-associated protein
• Cytoskeletal Proteins
• Interleukin-8
• MIRN320 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Tumor Necrosis Factor-alpha
• Glucose

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Cell Line
• Cytoskeletal Proteins (genetics, metabolism)
• Diabetic Nephropathies (metabolism)
• Glucose (metabolism, toxicity)
• Humans
• Interleukin-8 (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• RNA, Long Noncoding (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)