Cell apoptosis and proliferation in rat brains after intracerebral hemorrhage: role of Wnt/β-catenin signaling pathway

Background/Aims: The purpose of this study is to explore the immunoregulatory role of microRNA-21 (miR-21) targeting of the TLR4/MyD88 signaling pathway in macrophages in response to Bacillus Calmette-Guerin (BCG) infection. Methods: After infection with BCG, mouse RAW246.7 cells were assigned into control, BCG, miR-21 mimic + BCG, mimic-negative control (NC) + BCG, miR-21 inhibitor + BCG, inhibitor-NC + BCG, BCG + TAK242 (an inhibitor of the TLR4 signaling pathway), and miR-21 inhibitor + TAK242 + BCG groups. Western blotting and qRT-PCR were used to detect the expression of miR-21, TLR4 and MyD88. The levels of TNF-a, IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA). Cell viability was measured using an MTT assay. Cell apoptosis and necrosis rates were detected using flow cytometry. Results: Compared with the control group, miR-21 expression and levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were elevated, while expression of TLR4 and MyD88, as well as cell viability, were reduced in BCG infection groups. Compared with the BCG group, miR-21 expression was increased in the miR-21 mimic + BCG group but decreased in the miR-21 inhibitor + BCG and miR-21 inhibitor + TAK242 + BCG groups. The expression of TLR4 and MyD88, as well as the cell viability, were decreased, while levels of TNF-a, IL-6 and IL-10, as well as cell apoptosis and necrosis rates, were increased in the miR-21 mimic + BCG and TAK242 + BCG groups. The opposite trends were found in the miR-21 inhibitor + BCG group. Compared with the TAK242 + BCG group, the miR-21 inhibitor + TAK242 + BCG group had higher expression of TLR4 and MyD88 as well as higher cell viability and lower levels of TNF-a, IL-6, IL-10, cell apoptosis and necrosis rates. However, the miR-21 inhibitor + TAK242 + BCG group exhibited the opposite trends when compared with the miR-21 inhibitor + BCG group. Conclusion: Our results suggest that miR-21 can negatively modulate the TLR4/MyD88 signaling pathway, resulting in decreased cell viability, increased cell apoptosis and increased levels of inflammatory factors following BCG infection in macrophages.

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Role of flunarizine hydrochloride in secondary brain injury following intracerebral hemorrhage in rats

International Journal of Immunopathology and Pharmacology ◽

10.1177/0394632017742224 ◽

2017 ◽

Vol 30 (4) ◽

pp. 413-419 ◽

Cited By ~ 4

Author(s):

Jianping Niu ◽

Rui Hu

Keyword(s):

Brain Injury ◽

Intracerebral Hemorrhage ◽

Water Content ◽

Cell Apoptosis ◽

Akt Pathway ◽

Secondary Brain Injury ◽

Brain Water Content ◽

Hematoma Volume ◽

Brain Water

This study aimed to explore the role and mechanism(s) of flunarizine hydrochloride in the intracerebral hemorrhage (ICH) rats. The 32 adult male Sprague Dawley (SD) rats were randomly assigned into four groups: control group, sham group, ICH group, and FLU + ICH group. The effects of flunarizine hydrochloride were assessed on the basis of hematoma volume, blood–brain barrier (BBB) integrity, and brain water content in the ICH rat models. The role of flunarizine hydrochloride in cell recovery was assessed by behavioral scores, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot assay. Involvement of PI3K/AKT pathway in exerting the effect of flunarizine hydrochloride was also determined. Results showed that the hematoma volume, BBB integrity, and brain water content were significantly decreased in the FLU + ICH group. Cell apoptosis significantly increased in the ICH model group, while flunarizine hydrochloride decreased this increase. The expressions of glial cell line-derived neurotrophic factor (GDNF), neuroglobin (NGB), and p-AKT were increased after flunarizine hydrochloride treatment in ICH rats. In conclusion, flunarizine hydrochloride has protective effects against ICH by reducing brain injury, cell apoptosis, and the activation of P13K/AKT pathway. These findings provide a theoretical basis for the treatment of flunarizine hydrochloride in ICH.

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Identification of Candidate Blood mRNA Biomarkers in Intracerebral Hemorrhage Using Integrated Microarray and Weighted Gene Co-expression Network Analysis

Frontiers in Genetics ◽

10.3389/fgene.2021.707713 ◽

2021 ◽

Vol 12 ◽

Author(s):

Feng Jin ◽

Lei Li ◽

Yuehan Hao ◽

Ling Tang ◽

Yuye Wang ◽

...

Keyword(s):

Functional Analysis ◽

Network Analysis ◽

Intracerebral Hemorrhage ◽

Signaling Pathway ◽

Peripheral Blood ◽

Cell Apoptosis ◽

Expression Profiles ◽

Control Group ◽

High Morbidity ◽

Blood Draw

PurposeIntracerebral hemorrhage (ICH) is a serious public health hazard due to its high morbidity, disability, and mortality. Currently, the exact molecular mechanisms of ICH are unknown. We tried to identify the ICH-related candidate blood messenger RNA (mRNA) biomarkers by microarray analysis and weighted gene co-expression network analysis (WGCNA).Materials and MethodsWe collected the blood samples from patients with ICH (n = 4) and from vascular risk factor (VRF) controls (n = 4) and analyzed the mRNA expression profiles by competitive endogenous RNA (ceRNA) microarray. Differentially expressed genes (DEGs) were identified and then a weighted gene co-expression network was constructed. Modules with clinical significance were distinguished. Then, we downloaded two Gene Expression Omnibus (GEO) datasets (GSE24265 and GSE125512). Candidate mRNAs were identified by taking the intersection of the DEGs in our microarray, the interesting genes in the key module, and the DEGs in GSE24265. Functional analysis involving Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) and construction of a protein–protein interaction (PPI) network were conducted.ResultsA total of 340 DEGs in our microarray were identified between the ICH group and the control group. Among the eight gene modules established by WGCNA, the yellow module containing 191 genes was the most strongly associated with ICH. Four candidate mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) were identified. In the early stage of ICH (within 24 h), C3AR1, PAWR, and ARNTL2 were highly expressed in the perihematomal tissue, but with low expressions in peripheral blood; in the late stage (72 h after the first blood draw), an obvious upward trend of C3AR1 and PAWR in peripheral blood was seen. Functional analysis showed that candidate mRNAs were concerned with multiple pathways, such as the Wnt signaling pathway and calcium signaling pathway. They might affect the process of ICH through neuroinflammation, cell apoptosis, and pyroptosis.ConclusionWe identified four candidate blood mRNAs (C3AR1, PAWR, ARNTL2, and LDLRAD4) related to ICH. They showed different expression patterns in peripheral blood and perihematomal tissues and changed with time. They might play important roles in ICH through neuroinflammation, cell apoptosis, and pyroptosis and might shed new light to novel biomarkers or therapeutic targets in ICH.

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Overexpression of long non-coding RNA LINC00982 suppresses cell proliferation and tumor growth of papillary thyroid carcinoma through PI3K-ATK signaling pathway

Bioscience Reports ◽

10.1042/bsr20191210 ◽

2019 ◽

Vol 39 (7) ◽

Cited By ~ 1

Author(s):

Debin Xu ◽

Jichun Yu ◽

Shimin Zhuang ◽

Shuyong Zhang ◽

Zhengdong Hong ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Expression Levels ◽

And Migration ◽

Proliferation And Migration

Abstract Long non-coding RNAs (lncRNAs) have been widely reported that involved in human cancers, including papillary thyroid carcinoma (PTC). The present study aims to investigate the biological role of LINC00982 in PTC. The mRNA expression of LINC00982 in human PTC tissues was detected using qPCR. Moreover, Kaplan–Meier method was performed to analyze the internal relevance between LINC00982 expression and overall survival (OS) rate of patients with PTC. In addition, gain- and loss-of-functions assays were performed to detect the effects of LINC00982 on the cell proliferation and migration in PTC cells. Furthermore, western blot assay was used to measure the alteration expression levels of apoptosis relative proteins and the relative protein involved phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Finally, a xenograft model was used to analyze the antitumor role of LINC00982 in vivo. Here, we found that LINC00982 was decreased in human PTC tissues. Patients with decreased LINC00982 expression levels had a reduced OS (P=0.0019) compared with those with high LINC00982 expression levels. Overexpression of LINC00982 suppressed the proliferation and migration of BHT101 and B-CPAP cells and promoted cell apoptosis. Knockdown of LINC00982 promoted the proliferation and migration of BHT101 and B-CPAP cells and induced cell apoptosis. Moreover, in vivo assay showed that overexpression of LINC00982 could suppress the growth of PTC. Finally, LINC00982 could regulate the activity of PI3K/AKT signaling pathway in vitro and in vivo. Taken together, our findings demonstrated that overexpression of LINC00982 could suppress cell proliferation and induce cell apoptosis by regulating PI3K/AKT signaling pathway in PTC.

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Role of p75 neurotrophin receptor in neuronal autophagy in intracerebral hemorrhage in rats through the mTOR signaling pathway

Cell Cycle ◽

10.1080/15384101.2019.1711318 ◽

2020 ◽

Vol 19 (3) ◽

pp. 376-389

Author(s):

Lei Wang ◽

Meilei Tian ◽

Yugui Hao

Keyword(s):

Intracerebral Hemorrhage ◽

Signaling Pathway ◽

Mtor Signaling ◽

Neurotrophin Receptor ◽

P75 Neurotrophin Receptor ◽

Mtor Signaling Pathway ◽

Neuronal Autophagy

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SIRT5 regulates autophagy and apoptosis in gastric cancer cells

Journal of International Medical Research ◽

10.1177/0300060520986355 ◽

2021 ◽

Vol 49 (2) ◽

pp. 030006052098635

Author(s):

Wen Gu ◽

Qinyi Qian ◽

Yinkai Xu ◽

Xiaolan Xu ◽

Liping Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Mammalian Target Of Rapamycin ◽

Gastric Cancer Cells ◽

Protein Levels ◽

Amp Activated Protein Kinase ◽

Related Proteins

Objective Accumulating evidence illustrates that sirtuins (SIRTs) regulate autophagy and apoptosis in cancer cells; however, the role of SIRT5 in gastric cancer (GC) cells remains unknown. In this study, we examined the role of SIRT5 in GC cells. Methods We detected SIRT5 protein levels in freshly collected samples from patients with GC. Next, we studied the function of SIRT5 in autophagy. Furthermore, the signaling pathway through which SIRT5 enhanced autophagy in GC cells was detected. In addition, we established a GC cell apoptosis model to analyze the role of SIRT5 in apoptosis. Results SIRT5 expression was downregulated in GC tissues. We discovered that SIRT5 promoted autophagy in GC cells. We demonstrated that SIRT5 enhanced autophagy in GC cells via the AMP-activated protein kinase–mammalian target of rapamycin signaling pathway. In addition, SIRT5 was degraded during apoptosis in GC cells. Meanwhile, we observed that calpains and caspase-related proteins were associated with SIRT5-related GC cell apoptosis. Conclusions SIRT5 is a crucial regulator of autophagy and apoptosis in GC cell lines that can maintain the balance of autophagy and apoptosis.

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LncRNA gas5 regulates granulosa cell apoptosis and viability following radiation by X-ray through sponging miR-205-5p and Wnt/β-catenin signaling pathway ingranulosa cell tumor of ovary

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i12.2 ◽

2021 ◽

Vol 19 (12) ◽

pp. 2491-2498

Author(s):

Yan Li ◽

Xing Ma ◽

Jun Li ◽

Saifei He ◽

Juhua Zhuang ◽

...

Keyword(s):

Western Blot ◽

Cell Viability ◽

Signaling Pathway ◽

Granulosa Cell ◽

Cell Apoptosis ◽

Cell Tumor ◽

Luciferase Assay ◽

X Ray ◽

Lncrna Gas5

Purpose: The study explored the role of lncRNA gas5 in ovarian granulosa cells exposed to X-ray in granulosa cell tumor of ovary(GCTO). Methods:Exposed the KGN cell line (KALANG, Beijing, China) to X-ray to mimic the radiotherapy for GCSO patients in vitro, cell viability was checked by CCK8 assays. RT-qPCR detected the RNA expression of apoptosis-related genes while Western Blot for biomarkers in wnt/β-catenin signaling. Differential expressions of lncRNA gas5 were examined after cells exposed to X ray for 0,24,48hs. We over expressed gas5 and assessed resultant cell viabilities, apoptosis and signaling. The sponging between gas5 and miR-205-5p was verified through Luciferase Assay. CCK8, RT-qPCR and Western Blot were applied for investigations into the correlation between miR-205-5p and cell viability and apoptosis after miR-205-5p augmentation. Similarly, the interactions between the gas5 and miR-205-5p were assessed after co-transfection of miR-205-5p mimics and oe-gas5. Last, wnt inhibitor was used to study the role of signaling pathway in KGN cells. Results: Exposure of KGN toX-ray reduced cell viabilities and increased apoptosis. Gas5 had reduced expression in cells while miR-205-5p increased. Gas5 upregulation could protect the cells from apoptosis and add to the cell viability and activation of wnt//β-catenin signaling. lncRNA gas5 targeted miR-205-5p and miR-205-5p mimics could counteract functions of up-regulated lncRNA gas5, regulating Wnt/β-catenin signaling pathway. Inactivation in Wnt/β-catenin could suppress cell viability. Conclusions: lncRNA gas5 regulated the cell apoptosis and viability after cellular radiation, which might be a potential therapeutic target to combine into radiotherapy for GCTO patients in clinical stage. Keywords: Ovary, proliferation, apoptosis, lncRNA gas5, x-ray

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microR-505/heterogeneous nuclear ribonucleoprotein M inhibits hepatocellular carcinoma cell proliferation and induces cell apoptosis through the Wnt/β-catenin signaling pathway

Biomarkers in Medicine ◽

10.2217/bmm-2019-0511 ◽

2020 ◽

Vol 14 (11) ◽

pp. 981-996

Author(s):

Xiaobin Chi ◽

Yi Jiang ◽

Yongbiao Chen ◽

Lizhi Lv ◽

Jianwei Chen ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Proliferation ◽

Signaling Pathway ◽

Cell Apoptosis ◽

Heterogeneous Nuclear Ribonucleoprotein ◽

Apoptosis Assay ◽

Proliferation And Metastasis ◽

Novel Strategy ◽

Nuclear Ribonucleoprotein

Aim: This study aimed to investigate the expression of microRNA-505 (miR-505) and explore its clinical significance, biological function and mechanisms in hepatocellular carcinoma (HCC). Methods: Expression of miR-505 was measured in 128 paired HCC tissues and five cell lines by quantitative real-time polymerase chain reaction (qRT-PCR). MTT assay, Transwell migration, invasion assays and apoptosis assay were performed to explore the functional role of miR-505. The target gene of miR-505 was assessed using the bioinformatics assay and the related signaling pathway was confirmed using western blot. Results: Expression of miR-505 in HCC serum and tissues were downregulated. The overexpression of miR-505 in HCC cells inhibited cell proliferation and metastasis, as well as enhanced cell apoptosis by directly downregulating heterogeneous nuclear ribonucleoprotein M ( HNRNPM). The activity of the Wnt/β-catenin signaling pathway was suppressed by the overexpression of miR-505 but was promoted by the upregulation of HNRNPM. Conclusion: The results suggest that the regulation of miR-505/ HNRNPM may be a novel strategy to improve the targeted therapy of HCC.

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