Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy

Exp Cell Res. 2017 Jan 15;350(2):327-335. doi: 10.1016/j.yexcr.2016.12.006. Epub 2016 Dec 10.


Diabetic nephropathy is a common kidney condition in patients with diabetes mellitus, which can result in renal failure. Pyroptosis, the process of pro-inflammatory programmed cell death, plays an important role in the pathogenesis of this disease. Long non-coding RNA MALAT1 has also been shown to be involved in diabetic nephropathy. Here, we investigated the role of MALAT1 and the microRNA miR-23c and its target gene ELAVL1 in renal tubular epithelial cells. Our data demonstrated that MALAT1 expression was substantially increased but miR-23c was decreased in streptozotocin-induced diabetic rats and in high-glucose-treated HK-2 cells. Downregulation of MALAT1 or upregulation the expression of miR-23c inhibited pyroptosis in HK-2 cells. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic properties of MALAT1 and the anti-pyroptotic properties of miR-23c, we found that inhibiting the expression of MALAT1 downregulated the expression of ELAVL1, NLRP3, Caspase-1 and the pro-inflammatory cytokine IL-1β. These findings were replicated by upregulation of miR-23c. Moreover, luciferase assays showed that miR-23c, as a target of MALAT1, directly repressed ELAVL1 expression and then decreased the expression of its downstream protein NLRP3. The expression of MALAT1 antagonized the effect of miR-23c on the downregulation of its target ELAVL1 and inhibited hyperglycemia-induced cell pyroptosis. This mechanism may contribute to a better understanding of diabetic nephropathy pathogenesis and facilitate the development of new therapeutic strategies for the treatment of this disease.

Keywords: Diabetic nephropathy; Long non-coding RNA; MALAT1; MiR-23c; Pyroptosis.

MeSH terms

  • Animals
  • Caspase 1 / genetics
  • Caspase 1 / metabolism
  • Cell Line
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • ELAV-Like Protein 1 / genetics*
  • ELAV-Like Protein 1 / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism
  • MicroRNAs / genetics*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Pyroptosis*
  • RNA, Long Noncoding / genetics*
  • Rats
  • Rats, Sprague-Dawley


  • ELAV-Like Protein 1
  • Interleukin-1beta
  • MALAT1 long noncoding RNA, rat
  • MicroRNAs
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, rat
  • RNA, Long Noncoding
  • mirn21 microRNA, rat
  • Caspase 1