Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma

Chu, Qun; Jiang, Yanan; Zhang, Wei; Xu, Chaoqian; Du, Weijie; Tuguzbaeva, Gulnara; Qin, Ying; Li, Anqi; Zhang, Liangshuan; Sun, Guoxiang; Cai, Yongqiao; Feng, Qiang; Li, Guiyang; Li, Yanyao; Du, Zhenhong; Bai, Yunlong; Yang, Baofeng

doi:10.18632/oncotarget.12384

Cited by 130 publications

(107 citation statements)

References 20 publications

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“…to the previous studies [19,20]. The cells were transfected with small interfering RNA (siRNA) against Kcnq1ot1 (si-Kcnq1ot1), miR-214-3p mimics (miR-214-3p), the anti-miRNA oligonucleotide of miR-214-3p (AMO-214-3p) or the corresponding scrambled negative control (si-NC, NC, AMO-NC), which were designed and synthesized by RIOBIO (Guangzhou, China) using X-treme GENE siRNA transfection reagent (Roche, Germany).…”

Section: Cellular Physiology and Biochemistrysupporting

confidence: 63%

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Yang

Qin

Wang

et al. 2018

Cell Physiol Biochem

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142

109

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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.

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Section: Cellular Physiology and Biochemistrysupporting

confidence: 63%

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

Yang

Qin

Wang

et al. 2018

Cell Physiol Biochem

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142

109

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“…We also suggest that IL1 β from activated hepatocytes stimulates KCs to secret cytokines, which, in turn, promotes proliferation of hepatocytes. There is growing evidence that inflammasome activation is a major contributor to hepatocellular damage and results in different human and experimental liver diseases, including alcoholic steatohepatitis, chronic hepatitis C virus infection, ischemia‐reperfusion injury, and cancer . Our study suggests a mechanistic link between mitophagic modulation of inflammatory response and tumorigenesis, and further implies that FUNDC1‐mediated mitophagy may potentially represent a therapeutic target during the early stage of tumorigenesis.…”

Section: Discussionmentioning

confidence: 58%

FUN14 Domain‐Containing 1–Mediated Mitophagy Suppresses Hepatocarcinogenesis by Inhibition of Inflammasome Activation in Mice

et al. 2019

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Our results uncover that FUNDC1 suppresses HCC initiation by reducing inflammasome activation and inflammatory responses in hepatocytes, while up-regulation of FUNDC1 expression at the late stage of tumor development may benefit tumor growth. Our study thus provides a mechanistic link between mitophagic modulation of the inflammatory response and tumorigenesis, and further implies that FUNDC1-mediated mitophagy and its related inflammatory response may represent a therapeutic target for liver cancer. This article is protected by copyright. All rights reserved.

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“…Therefore, it will be meaningful to evaluate coptisine's effect on cellular senescence of cancer cells. Another essential issue which needs to be further detected in future investigation is the role of coptisine to act as small‐molecule inhibitor of key markers involved in inflammation, CVDs, etc Berberine is revealed to diminish mRNA overexpression of caspase‐1 and NLRP3 in MSU‐challenged Raw 264.7 cells, and it also regulates pyroptosis in human hepatocellular carcinoma . Since caspase‐1 is a key marker participating in inflammasome assembling and pyroptosis occurrence, and coptisine displays considerable suppressing effect on NLRP3 inflammasome priming and assembly, another relevant subject for further study can be the role of coptisine as small‐molecular inhibitor of caspase‐1 and the downstream pyroptosis activation.…”

Section: Future Prospectsmentioning

confidence: 99%

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma

Cited by 130 publications

References 20 publications

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

LncRNA KCNQ1OT1 Mediates Pyroptosis in Diabetic Cardiomyopathy

FUN14 Domain‐Containing 1–Mediated Mitophagy Suppresses Hepatocarcinogenesis by Inhibition of Inflammasome Activation in Mice

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

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