Down‐regulation of GAS5 ameliorates myocardial ischaemia/reperfusion injury via the miR‐335/ROCK1/AKT/GSK‐3β axis

Wu, Nan; Zhang, Xiaowen; Bao, Yandong; Yu, Hao; Jia, Dalin; Ma, Chao

doi:10.1111/jcmm.14724

Cited by 59 publications

(58 citation statements)

References 34 publications

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“…For instance, GAS5 was upregulated in atherosclerosis, suggesting that GAS5 implicated in the development of atherosclerosis [22]. Moreover, the expression levels of GAS5 remarkably increased in epilepsy and ischemic heart disease [23,24]. Additionally, in this study, we found that GAS5 expression signi cantly downregulated in osteosarcoma, which was also consistent with some reports.…”

Section: Discussionsupporting

confidence: 91%

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

Liu¹,

Chen²,

Ma³

et al. 2020

Preprint

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Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and non-malignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and downregulated miR-23a-3p that post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo . Conclusion: GAS5 functions as a competing endogenous RNA , sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

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Section: Discussionsupporting

confidence: 91%

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

Liu¹,

Chen²,

Ma³

et al. 2020

Preprint

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“…Therefore, miR-335 disturbed proliferation and migration, while promoting radiosensitivity of melanoma by inhibiting ROCK1. The miR-335/ROCK1 axis regulated multiple functions, including tumor progression (19)(20)(21), myocardial ischemia/reperfusion (22), and chondrogenesis (23). Lynch and colleagues firstly illustrated the negative feedback loop among miR-335/ROCK1-noncanonical TGF-β signaling and MYCN (24).…”

Section: Discussionmentioning

confidence: 99%

miR-335 Acts as a Tumor Suppressor and Enhances Ionizing Radiation-Induced Tumor Regression by Targeting ROCK1

Cheng

Shen

2020

Front. Oncol.

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Recent development of integrative therapy against melanoma combines surgery, radiotherapy, targeted therapy, and immunotherapy; however, the clinical outcomes of advanced stage and recurrent melanoma are poor. As a skin cancer, melanoma is generally resistant to radiotherapy. Hence, there is an urgent need for evaluation of the mechanisms of radioresistance. The present study identified miR-335 as one of the differential expression of miRNAs in recurrent melanoma biopsies post-radiotherapy. The expression of miR-335 declined in melanoma tissues compared to the adjacent tissues. Moreover, miR-335 expression correlated with advanced stages of melanoma negatively. Consistent with the prediction of STARBASE and miRDB database, miR-335 targeted ROCK1 via binding with 3 ′ -UTR of ROCK1 directly, resulting in attenuation of proliferation, migration, and radioresistance of melanoma cells. The authors validated that overexpression of miR-335 enhanced X-ray-induced tumor regression by B16 mouse models. Briefly, the present findings gained insights into miR-335/ROCK1-mediated radiosensitivity and provided a promising therapeutic strategy for improving radiotherapy against melanoma.

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“…Primary neonatal rat cardiomyocytes were isolated from 1-day-old Wistar rats and cultured as described in our previous study. 17 Briefly, neonatal rats were sacrificed by decapitation and hearts were harvested. The ventricles were further separated and minced into 1 mm 3 pieces, followed by digestion with 0.05% pancreatin and 0.01% collagenase.…”

Section: Primary Neonatal Rat Cardiomyocyte Culturementioning

confidence: 99%

<p>microRNA Expression Profiles in Myocardium of High-Fat Diet-Induced Obesity Rat</p>

Yang

Xin

et al. 2020

DMSO

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A high-fat diet (HFD) can lead to cardiac dysfunction, hypertrophy, and fibrosis. This study aimed to explore microRNA expression profiles in the myocardium of HFDinduced obesity rat. Materials and Methods: Wistar rats were randomly divided into two groups, and fed with normal chow diet (NCD) or HFD for 20 weeks. Cardiac function was evaluated by echocardiography. Left ventricular myocardium was harvested to assess the extent of myocardial morphology alteration. MicroRNA expression was analyzed using Agilent miRNA microarray and quantitative real-time PCR (qRT-PCR) was used to validate the microarray data. The mirdbV6 database was used to forecast the miRNA target genes. The role of microRNAs in palmitate-induced cardiac hypertrophy and fibrosis in primary neonatal rat cardiomyocytes was evaluated by loss-and gain-of-function experiments. Results: Significant changes in cardiac function, hypertrophy, fibrosis, and apoptosis were found in HFD rats as compared with NCD rats. miR-141-3p and miR-144-3p were also significantly upregulated in the myocardium of HFD-induced obesity rat. A series of genes involved in essential biological processes, including anatomical structure development and metabolic process, was targeted by these two miRNAs. These target genes were also implicated in signaling pathways involved in the PI3K-Akt signaling pathway, Wnt signaling pathway, autophagy, and protein processing in the endoplasmic reticulum. Inhibition of miR-141 or overexpression of miR-144 attenuated palmitate-induced cardiac hypertrophy and fibrosis. In contrast, overexpression of miR-141 or inhibition of miR-144 aggravated palmitate-induced cardiac hypertrophy and fibrosis. Conclusion: This study identifies that miR-141 and miR-144 are candidate miRNAs associated with the development of HFD-induced cardiac dysfunction and structure alteration.

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Down‐regulation of GAS5 ameliorates myocardial ischaemia/reperfusion injury via the miR‐335/ROCK1/AKT/GSK‐3β axis

Cited by 59 publications

References 34 publications

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

miR-335 Acts as a Tumor Suppressor and Enhances Ionizing Radiation-Induced Tumor Regression by Targeting ROCK1

<p>microRNA Expression Profiles in Myocardium of High-Fat Diet-Induced Obesity Rat</p>

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