Abstract: SA-PO993
Hypoxia-Inducible Long Non-Coding RNA, MIR210HG, Contributes to the Stability of HIF1α via miR-93-5p in Renal Tubular Epithelial Cells
Session Information
- CKD: Pathobiology - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Saigusa, Hanako, Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Bunkyo-ku, Tokyo, Japan
- Mimura, Imari, Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Bunkyo-ku, Tokyo, Japan
- Nangaku, Masaomi, Tokyo Daigaku Daigakuin Igakukei Kenkyuka Igakubu, Bunkyo-ku, Tokyo, Japan
Background
Chronic hypoxia in the renal tubular interstitium is involved in the progression of chronic kidney disease. Hypoxia inducible factor (HIF1α), which is considered to be the master transcriptional regulator of response to hypoxia, is also subject to various regulation. Recently, there have been increasing reports that non-coding RNAs such as micro RNA (miRNA)s and long non-coding RNA (lnc RNA)s regulate the expression of HIF1α.
Methods
We exposed human renal proximal tubular cell lines (RPTEC) to 1% O2 hypoxia for 1 to 48 hours, and examined the role of MIR210HG regulated by HIF1α.
Results
Micro RNA 210 host gene (MIR210HG) was up-regulated from 1 hour after the start of hypoxic stimulation, and maintained the rise until 48 hours. Knockdown of HIF1α decreased the expression of MIR210HG under hypoxia and the exposure of cobalt chloride promoted MIR210HG expression. Knockdown of MIR210HG significantly reduced both mRNA and protein levels of HIF1α, and promoted cell apoptosis. MiR-93-5p has the sequence predicted to bind to both MIR210HG and HIF1α and was previously reported to bind to HIF1α 3’ untranslated region. Knockdown of MIR210HG increased the expression of miR-93-5p, and overexpression of miR-93 reduced the level of both HIF1α and MIR210HG. Luciferase assay confirmed that miR-93-5p binds to MIR210HG directly.
Conclusion
We revealed that MIR210HG was induced shortly after hypoxia under the regulation by HIF1α, and also modulated HIF1α by competing for miR-93-5p. Under the chronic hypoxia in the renal tubular cells, MIR210HG plays an important role in the biological response to hypoxia and cell survival.
Funding
- Government Support – Non-U.S.