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LncRNA MIR503HG Promotes High-Glucose-Induced Proximal Tubular Cell Apoptosis by Targeting miR-503-5p/Bcl-2 Pathway

Xu Cao1, Qiu-Ling Fan1

  • 1Department of Nephrology, The First Hospital of China Medical University, Shenyang, People's Republic of China.

Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy
|December 2, 2020
PubMed
Abstract

Insights

The long non-coding RNA MIR503HG (miR-503 host gene) is co-transcribed with miR-503 and influences its splicing, impacting Bcl-2 expression and apoptosis in high-glucose conditions. This suggests MIR503HG is a potential therapeutic target for diabetic nephropathy.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Long non-coding RNAs (lncRNAs) can host microRNAs (miRNAs), influencing gene expression and cellular processes.
  • The interplay between lncRNAs, miRNAs, and their target genes is crucial for cellular homeostasis, particularly in disease states like diabetic nephropathy (DN).
  • The specific role of the lncRNA MIR503HG (miR-503 host gene) in regulating miR-503, its target gene Bcl-2, and the mitochondrial apoptotic pathway in DN remains unclear.

Purpose of the Study:

  • To investigate whether lncRNA MIR503HG is co-transcribed with miR-503.
  • To determine if MIR503HG affects miR-503 splicing and subsequently influences the expression of its target gene Bcl-2.
  • To elucidate the role of the MIR503HG/miR-503 axis in the mitochondrial apoptotic pathway in high-glucose-induced proximal tubular cells and its relevance to diabetic nephropathy.

Main Methods:

  • Human proximal tubular (HK-2) cells were cultured under high glucose conditions and transfected with MIR503HG or miR-503 overexpression/inhibition vectors.
  • Real-time quantitative PCR (RT-qPCR) was employed to quantify the expression levels of lncRNA MIR503HG, pre-miR-503, mature miR-503, and the target gene Bcl-2.
  • Western blotting and Annexin V/PI flow cytometry were utilized to assess protein expression related to apoptosis (Bcl-2, Bax, Cytc, cleaved-caspase 9/3) and quantify cell apoptosis rates.

Main Results:

  • Host lncRNA MIR503HG was found to be co-transcribed with miR-503, regulating miR-503 expression through its splicing.
  • High glucose upregulated both MIR503HG and miR-503 in HK-2 cells, leading to decreased Bcl-2 expression and increased apoptosis-related proteins (Bax, Cytc), ultimately promoting mitochondrial apoptosis.
  • Inhibition of MIR503HG reduced miR-503 levels, upregulated Bcl-2, decreased pro-apoptotic proteins, and attenuated high-glucose-induced apoptosis in HK-2 cells.

Conclusions:

  • MIR503HG indirectly regulates Bcl-2 expression by promoting the co-transcription and proper splicing of miR-503.
  • The MIR503HG/miR-503 axis plays a significant role in high-glucose-induced proximal tubular cell apoptosis, a key process in diabetic nephropathy.
  • MIR503HG represents a novel therapeutic target for managing diabetic nephropathy by modulating the mitochondrial apoptotic pathway.
Keywords:
apoptosisdiabetic nephropathyhost genelncRNA MIR503HGmiR-503

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