LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Abstract

Background/Aims: Diabetic cardiomyopathy (DCM) is a common complication of diabetes and can cause heart failure, arrhythmia and sudden death. The pathogenesis of DCM includes altered metabolism, mitochondrial dysfunction, oxidative stress, inflammation, cell death and extracellular matrix remodeling. Recently, pyroptosis, a type of programmed cell death related to inflammation, was proven to be activated in DCM. However, the molecular mechanisms underlying pyroptosis in DCM remain elusive. The long non-coding RNA (lncRNA) Kcnq1ot1 participates in many cardiovascular diseases. This study aims to clarify whether Kcnq1ot1 affects cardiac pyroptosis in DCM. Methods: AC16 cells and primary cardiomyocytes were incubated with 5.5 and 50 mmol/L glucose. Diabetic mice were induced with streptozotocin (STZ). Kcnq1ot1 was silenced both in vitro and in vivo. qRT-PCR was used to detect the expression level of Kcnq1ot1. Immunofluorescence, qRT-PCR and western blot analyses were used to detect the degree of pyroptosis. Echocardiography, hematoxylin and eosin staining, and Masson’s trichrome staining were used to detect the cardiac function and morphology in mice. Cell death and function were detected using TUNEL staining, immunofluorescence staining and Ca²⁺ measurements. Results: The expression of Kcnq1ot1 was increased in patients with diabetes, high glucose-induced cardiomyocytes and diabetic mouse cardiac tissue. Silencing Kcnq1ot1 alleviated pyroptosis by targeting miR-214-3p and caspase-1. Furthermore, silencing Kcnq1ot1 reduced cell death, cytoskeletal structure abnormalities and calcium overload in vitro and improved cardiac function and morphology in vivo. Conclusion: Kcnq1ot1 is overexpressed in DCM, and silencing Kcnq1ot1 inhibits pyroptosis by influencing miR-214-3p and caspase-1 expression. We clarified for the first time that Kcnq1ot1 could be a new therapeutic target for DCM.

LncRNA KCNQ1OT1 attenuates sepsis-induced myocardial injury via regulating miR-192-5p/XIAP axis

“…28 Interestingly, investigations have shown that KCNQ1OT1 was up-regulated in diabetes-induced cardiomyopathy, which can significantly accelerate apoptosis in diabeticinduced cardiomyopathy cells. 29 In the present work, we uncovered that KCNQ1OT1 was significantly decreased in the SIC model, and the gain-and loss-assay confirmed that KCNQ1OT1 inhibited the progression of sepsis-induced myocardial injury.…”

Melatonin exerts neuroprotective effects by inhibiting neuronal pyroptosis and autophagy in STZ‐induced diabetic mice

“…Our previous studies demonstrated that miR-214-3p is involved in regulating cardiac pyroptosis by binding to caspase-1. 28 Herein, we found that the level of miR-214-3p was decreased in the brains of DM mice and in HG-treated neuronal cells F I G U R E 4 MiR-214-3p regulates neuronal pyroptosis by targeting caspase-1. A, The levels of miR-214-3p in mice and neuronal cells as detected by real-time PCR.…”

Expression profiles of long noncoding RNAs in type 2 diabetes mellitus rat associated with the progression of ischemia-reperfursion injury

“…However, the research on myocardial I/R injury have received relatively little attention, and the complex mechanism and signal pathway involved in lncRNA still need to be further clari ed. Yang et al [16]con rmed that the expression of lncRNA Kcnq1ot1 was increased in cardiomyocytes induced by high glucose and cardiac tissues of DM mouse. Silencing Kcnq1ot1 moderated pyroptosis, reduced cell death, improved cytoskeleton structure abnormalities and calcium overload in vitro, and improved heart function and morphology in vivo.…”