microRNA‐802 accelerates hepatocellular carcinoma growth by targeting <i>RUNX3</i>

Ni, Min; Zhao, Yi; Zhang, Wenjing; Jiang, Yu‐Jie; Fu, Hui; Huang, Fang; Li, Dongjie; Shen, Fu‐Ming

doi:10.1002/jcp.29611

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…Moreover, miR-802 overexpression significantly inhibited while miR-802 knockdown promoted ZNF521 mRNA and protein in HCC cells ( P < 0.05, Figure 6 C-D). In HCC tissues, our results showed that miR-802 was up-regulated in HCC tissues compared to adjacent non-tumor tissues ( P < 0.05, Figure 6 E), which was consistent with previous studies 20 . We also confirmed an inverse correlation between ZNF521 mRNA and miR-802 in HCC tissues ( r =-0.7223, P < 0.05, Figure 6 F).…”

Section: Resultssupporting

confidence: 92%

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ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

Yang¹,

Wang²,

Chen³

et al. 2020

J. Cancer

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Zinc finger protein 521 (ZNF521) plays an important role in the tumor development and process. However, its regulatory role in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated for the first time that ZNF521 mRNA and protein was down-regulated in HCC tissues and cell lines. Down-regulated ZNF521 expression was significantly associated with malignant prognostic features, including advanced TNM stage and large tumor size. For 5-year survival, ZNF521 served as a potential prognostic marker of HCC patients. Moreover, ZNF521 inhibited cell proliferation, colony formation and cell viability through Runx2 transcriptional inhibition and AKT phosphorylation pathway. Moreover, we demonstrated that ZNF521 expression was regulated by miR-802. In HCC tissues. MiR-802 has an inverse correlation with ZNF521 expression. In conclusion, we demonstrate for the first time that ZNF521 is down-regulated in HCC tissues and inhibits HCC growth through Runx2 transcriptional inhibition and AKT inactivation, which was regulated by miR-802, suggesting the potential therapeutic value for HCC.

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Section: Resultssupporting

confidence: 92%

“…miR-802 negatively regulated the expression of ZNF521 mRNA and protein in HCC cells. Previous studies reported that miR-802 accelerates hepatocellular carcinoma growth by targeting Runx3 [20]. High blood miR-802 is associated with poor prognosis in HCC patients by regulating DNA damage response 1 (REDD1)mediated function of T cells [31].…”

Section: Discussionmentioning

confidence: 99%

ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

Yang¹,

Wang²,

Chen³

et al. 2020

J. Cancer

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“…Recently, Zhang et al [68] demonstrated miR-802's ability to inhibit the aggressive behaviors of non-small cell lung cancer cells. However, it has also been described that miR-802 can accelerate the growth of hepatocellular carcinoma (HCC) [69] and that its high concentration in blood is associated with a poor prognosis in HCC patients [70]. Furthermore, miR-802 has been shown to partake in obesity-induced nephropathy in obese human and mice [71].…”

Section: Mir-802mentioning

confidence: 99%

Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance

Pielok

Marycz

2020

IJMS

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In the recent years, the prevalence of metabolic conditions such as type 2 Diabetes (T2D) and metabolic syndrome (MetS) raises. The impairment of liver metabolism resulting in hepatic insulin resistance is a common symptom and a critical step in the development of T2D and MetS. The liver plays a crucial role in maintaining glucose homeostasis. Hepatic insulin resistance can often be identified before other symptoms arrive; therefore, establishing methods for its early diagnosis would allow for the implementation of proper treatment in patients before the disease develops. Non-coding RNAs such as miRNAs (micro-RNA) and lncRNAs (long-non-coding RNA) are being recognized as promising novel biomarkers and therapeutic targets—especially due to their regulatory function. The dysregulation of miRNA and lncRNA activity has been reported in the livers of insulin-resistant patients. Many of those transcripts are involved in the regulation of the hepatic insulin signaling cascade. Furthermore, for several miRNAs (miR-802, miR-499-5p, and miR-122) and lncRNAs (H19 imprinted maternally expressed transcript (H19), maternally expressed gene 3 (MEG3), and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)), circulating levels were altered in patients with prediabetes, T2D, and MetS. In the course of this review, the role of the aforementioned ncRNAs in hepatic insulin signaling cascade, as well as their potential application in diagnostics, is discussed. Overall, circulating ncRNAs are precise indicators of hepatic insulin resistance in the development of metabolic diseases and could be applied as early diagnostic and/or therapeutic tools in conditions associated with insulin resistance.

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“…MiR-802 possesses multiple function. It has been reported to regulate cancer development, alleviate lipopolysaccharide (LPS)-induced acute lung injury, and modulate the expression of human angiotensin II type I receptor [38][39][40]. In the term of metabolism, miR-802 impairs glucose metabolism and causes nephropathy in both obese mice and human [41,42].…”

Section: Discussionmentioning

confidence: 99%

Hypertrophic adipocyte-derived exosomal miR-802-5p contributes to insulin resistance in cardiac myocytes through targeting HSP60

Wen

et al. 2020

Preprint

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Background : Epicardial adipose tissue (EAT) is implicated in insulin resistance, which has been recognized as a strongest predictor of the development of diabetic cardiomyopathy and subsequent heart failure. However, the underlying mechanism remains incompletely understood. Herein, we investigated the effect of hypertrophic adipocytes on cardiac insulin resistance. Methods : Palmitate was used to induce hypertrophic 3T3-L1 adipocytes. Exosomes were purified from normal control or hypertrophic 3T3-L1 adipocyte-associated conditioned medium. Exosome-exposed neonatal rat ventricular myocytes (NRVMs) were treated with insulin to investigate the effects of exosomes on insulin signaling. Insulin sensitivity was evaluated by measuring insulin-stimulated Akt phosphorylation and glucose uptake. SiRNA techniques were used to downregulate protein levels and its efficiency was evaluated by western blot.Results : Hypertrophic adipocyte-derived exosomes (h-Exo) induced insulin resistance in NRVMs. Furthermore, h-Exo high-expressed miR-802-5p. Insulin sensitivity of NRVMs was impaired by miR-802-5p mimic but improved by its inhibitor. TargetScan and luciferase reporter assays revealed that heat shock protein 60 (HSP60) was a direct target of miR-802-5p. Both h-Exo and miR-802-5p mimic could downregulate HSP60 protein levels. In addition, HSP60 silencing induced insulin resistance and mitigated the insulin-sensitizing effects of adiponectin. HSP60 depletion also significantly increased the expression levels of CHOP, a marker of the unfolded protein response (UPR), and enhanced oxidative stress, accompanied by the increased phosphorylation of JNK and IRS-1 Ser307. Inhibition of both miR-802-5p and endocytosis abolished the impacts of HSP60 knockdown on the UPR and oxidative stress. Conclusion : Hypertrophic adipocyte-derived exosomal miR-802-5p caused cardiac insulin resistance in NRVMs through downregulating HSP60. These findings provide a novel mechanism by which EAT impairs cardiac function.

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microRNA‐802 accelerates hepatocellular carcinoma growth by targeting RUNX3

Cited by 15 publications

References 35 publications

ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

ZNF521 which is downregulated by miR-802 suppresses malignant progression of Hepatocellular Carcinoma through regulating Runx2 expression

Non-Coding RNAs as Potential Novel Biomarkers for Early Diagnosis of Hepatic Insulin Resistance

Hypertrophic adipocyte-derived exosomal miR-802-5p contributes to insulin resistance in cardiac myocytes through targeting HSP60

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