scholarly journals miR-135b Plays a Neuroprotective Role by Targeting GSK3β in MPP+-Intoxicated SH-SY5Y Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Jianlei Zhang ◽  
Wei Liu ◽  
Yabo Wang ◽  
Shengnan Zhao ◽  
Na Chang
Keyword(s):  
Cell Proliferation ◽  
Glycogen Synthase ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Inflammatory Cytokine Production ◽  
Protein Levels

miR-135a-5p was reported to play a crucial role in the protective effects of hydrogen sulfide against Parkinson’s disease (PD) by targeting rho-associated protein kinase 2 (ROCK2). However, the role of another member of miR-135 family (miR-135b) and the underlying mechanism in PD are still unclear. qRT-PCR and western blot showed that miR-135 was downregulated and glycogen synthase kinase 3β (GSK3β) was upregulated at mRNA and protein levels in MPP+-intoxicated SH-SY5Y cells in a dose- and time-dependent manner. MTT, TUNEL, and ELISA assays revealed that miR-135b overexpression significantly promoted cell proliferation and inhibited apoptosis and production of TNF-α and IL-1β in SH-SY5Y cells in the presence of MPP+. Luciferase reporter assay demonstrated that GSK3β was a direct target of miR-135b. Moreover, sodium nitroprusside (SNP), a GSK3β activator, dramatically reversed the effects of miR-135b upregulation on cell proliferation, apoptosis, and inflammatory cytokine production in MPP+-intoxicated SH-SY5Y cells. Taken together, miR-135b exerts a protective role via promotion of proliferation and suppression of apoptosis and neuroinflammation by targeting GSK3β in MPP+-intoxicated SH-SY5Y cells, providing a potential therapeutic target for the treatment of PD.

scholarly journals Lentivirus-Mediated siRNA Targeting ER-αInhibits Tumorigenesis and Induces Apoptosis in Hepatocarcinoma Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Jiang ◽  
Jun Cao ◽  
Wen-Hui Bai
Keyword(s):  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Dependent Manner ◽  
Gene Therapy Approach ◽  
Protein Levels ◽  
Human Liver Cancer ◽  
Hepatocarcinoma Cells ◽  
Interfering Rna ◽  
Hcc Cells

Background and Objectives. Estrogen receptor-α(ER-α) plays important roles in hepatocarcinogenesis. Recent studies have shown that ER-αcould lead to cell cycle progression or inhibition of apoptosis. To better understand the role of ER-α, RNA interference (RNAi) was used to inhibit ER-αexpression in the human hepatocellular carcinoma (HCC) cells.Methods. Lentivirus-mediated ER-αsmall interfering RNA (siRNA) was transfected into HCC cells Hep3B. ER-αexpression was monitored by real-time polymerase chain reaction (PCR) and western blot. Cell proliferation, apoptosis, and invasion were examined by methyl thiazol tetrazolium (MTT), flow cytometry (FCM), and invasion assay, respectively.Results. ER-αsiRNA efficiently downregulated the expression of ER-αin Hep3B cells at both mRNA and protein levels in a time-dependent manner. ER-αsiRNA also inhibited cell proliferation and reduced cell invasion (compared with other groups,P<0.05, resp.). Furthermore, knockdown of ER-αslowed down the cell population at S phase and increased the rate of apoptosis (P<0.05, resp.).Conclusion. ER-αknockdown suppressed the growth of HCC cells. Thus, ER-αmay play a very important role in carcinogenesis of HCC and its knockdown may offer a new potential gene therapy approach for human liver cancer in the future.

CSN5 promotes carcinogenesis of thyroid carcinoma cells through ANGPTL2

Endocrinology ◽  
2020 ◽  
Author(s):  
Peiyi Xie ◽  
Hui Wang ◽  
Jiayu Fang ◽  
Dongnian Du ◽  
Ze Tian ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Thyroid Carcinoma ◽  
Carcinoma Cell ◽  
Underlying Mechanism ◽  
Protein Levels ◽  
Proliferation And Metastasis ◽  
Gain Loss ◽  
Thyroid Carcinoma Cell ◽  
Cell Proliferation And Metastasis

Abstract COP9 signalosome subunit 5 (CSN5) plays a key role in carcinogenesis of multiple cancers, and contributes to stabilization of target proteins through deubiquitylation. However, the underlying role of CSN5 in thyroid carcinoma has not been reported. In this research, our data showed that CSN5 was overexpressed in thyroid carcinoma tissues compared with para-cancerous tissues. Furthermore, a series of gain/loss functional assays were performed to demonstrate the role of CSN5 in facilitating thyroid carcinoma cell proliferation and metastasis. Additionally, we found that there was a positive correlation between CSN5 and angiopoietin-like protein 2 (ANGPTL2) protein levels in thyroid carcinoma tissues and that CSN5 promoted thyroid carcinoma cell proliferation and metastasis through ANGPTL2. We also identified the underlying mechanism that CSN5 elevated ANGPTL2 protein level through directly binding it, and decreasing its ubiquitination and degradation. Overall, our results highlight the significance of CSN5 in promoting thyroid carcinoma carcinogenesis and implicate CSN5 as a promising candidate for thyroid carcinoma treatment.

scholarly journals MiR-596 activated by EP300 controls the tumorigenesis in epithelial ovarian cancer by declining BRD4 and KPNA4

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Deying Wang ◽  
Yulan Cui ◽  
Aili Xu ◽  
Lin Zhao ◽  
Peiling Li
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Epithelial Ovarian Cancer ◽  
Luciferase Reporter ◽  
Past Study ◽  
Protein Levels ◽  
Promising Therapeutic Target ◽  
Advanced Stages

Abstract Background Epithelial ovarian cancer (EOC), a subclass of ovarian cancer (OC), is usually diagnosed at advanced stages due to the lack of effective screening means. Mounting reports have disclosed the vitally important roles of microRNAs (miRNAs) in carcinogenesis. Here, we aimed to find out possible miRNAs participating in EOC development. Methods qRT-PCR ad western blot respectively examined the mRNA and protein levels of studied genes. CCK-8, colony formation, flow cytometry, TUNEL and spheroid formation assays were appropriately employed for examining cell proliferation, cell cycle, apoptosis and stemness. The interaction between molecules was affirmed by luciferase reporter, RNA pull down and ChIP assays. Results In consistent with the observation of a past study, miR-596 expression was relatively low in EOC cells. Up-regulating miR-596 suppressed EOC cell proliferation and stemness. EP300 transcriptionally activated miR-596 to serve as a tumor-repressor in EOC. Then BRD4 and KPNA4, whose knockdown led to restraining effects on cell growth and stemness, were both revealed to be targeted by miR-596 in EOC. Lastly, rescue assays affirmed the tumor-restraining role of miR-596-BRD4/KPNA4 axis in EOC. Conclusion EP300-activated miR-596 hampered cell growth and stemness via targeting BRD4 and KPNA4 in EOC, proofing miR-596 as a promising therapeutic target in treating EOC patients.

scholarly journals IcarisideII facilitates the differentiation of ADSCs to SCs via let-7i/STAT3 axis to preserve erectile function

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Pingyu Ge ◽  
Yinxue Guo ◽  
Jun Shen
Keyword(s):  
Cell Proliferation ◽  
Erectile Function ◽  
Molecular Mechanisms ◽  
Therapeutic Option ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Regulatory Relationship ◽  
Rat Models ◽  
Protein Levels ◽  
Dose Dependent

Abstract Background IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. Methods ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. Results ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. Conclusion ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.

scholarly journals MicroRNA-222 alleviates radiation-induced apoptosis by targeting BCL2L11 in cochlea hair cells

2021 ◽  
Author(s):  
Yan-yan Zhang ◽  
Gao-yun Xiong ◽  
Xiao-xing Xie
Keyword(s):  
Dna Damage ◽  
Hair Cell ◽  
Cell Injury ◽  
Biological Effects ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Protective Effects ◽  
Radiation Induced ◽  
Induced Apoptosis

Radiation-induced hair cell injury is detrimental for human health but the underlying mechanism is not clear. MicroRNAs (miRNAs) have critical roles in various types of cellular biological processes. The present study investigated the role of miR-222 in the regulation of ionizing radiation (IR)-induced cell injury in auditory cells and its underlying mechanism. Real time PCR was performed to identify the expression profile of miR-222 in the cochlea hair cell line HEI-OC1 after IR exposure. miRNA mimics or inhibitor-mediated upregulation or downregulation of indicated miRNA was applied to characterize the biological effects of miR-222 using MTT, apoptosis and DNA damage assay. Bioinformatic analyses and luciferase reporter assays were applied to identify a miRNA target gene. Our study confirmed that IR treatment significantly suppressed miR-222 levels in a dose-dependent manner. Upregulation of miR-222 enhances cell viability and alleviated IR-induced apoptosis and DNA damage in HEI-OC1 cells. In addition, BCL-2-like protein 11 (BCL2L11) was validated as a direct target of miR-222. Overexpression of BCL2L11 abolished the protective effects of miR-222 in IR-treated HEI-OC1 cells. Moreover, miR-222 alleviated IR-induced apoptosis and DNA damage by directly targeting BCL2L11.The present study demonstrates that miR-222 exhibits protective effects against irradiation‑induced cell injury by directly targeting BCL2L11 in cochlear cells.

scholarly journals CircCDC45 promotes the malignant progression of glioblastoma by modulating the miR-485-5p/CSF-1 axis

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rongcai Liu ◽  
Weimin Dai ◽  
An Wu ◽  
Yunping Li
Keyword(s):  
Cell Proliferation ◽  
Cancer Progression ◽  
Biological Effects ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Invasion And Migration ◽  
Protein Levels

Abstract Background Glioblastoma (GBM) is characterized by progressive growth and metastasis. Numerous studies claim that the deregulation of circular RNAs (circRNAs) is associated with cancer progression. However, the role of circRNAs in GBM is largely limited. The purpose of this study was to investigate the functions of circCDC45 in GBM and provide a feasible functional mechanism to support its role. Methods The expression of circCDC45, miR-485-5p and colony-stimulating factor 1 (CSF-1) mRNA was examined using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit − 8 (CCK-8) assay and colony formation assay. Cell migration and cell invasion were monitored using transwell assay. The protein levels of proliferation-related markers and CSF-1 were determined using western blot. The target relationship was predicted using bioinformatics tools and validated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Animal models were constructed to verify the role of circCDC45 in vivo. Results The expression of circCDC45 and CSF-1 was elevated in GBM tissues and cells, while the expression of miR-485-5p was declined. Downregulation of circCDC45 or CSF-1 blocked GBM cell proliferation, invasion and migration as well as tumor growth in vivo. In mechanism, circCDC45 positively regulated the expression of CSF-1 by targeting miR-485-5p. Inhibition of miR-485-5p reversed the biological effects caused by circCDC45 downregulation in GBM cells. Conclusion CircCDC45 promoted the progression of GBM by mediating the miR-485-5p/CSF-1 axis, and circCDC45 might be a promising plasmatic biomarker for GBM diagnosis and treatment.

scholarly journals MicroRNA-30e targets BNIP3L to protect against aldosterone-induced podocyte apoptosis and mitochondrial dysfunction

2017 ◽  
Vol 312 (4) ◽  
pp. F589-F598 ◽  
Author(s):  
Yan Guo ◽  
Xu Deng ◽  
Shuang Chen ◽  
Lingyun Yang ◽  
Jiajia Ni ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Early Event ◽  
Dependent Manner ◽  
Podocyte Injury ◽  
Interacting Protein ◽  
Adenovirus E1b ◽  
Induced Apoptosis

MicroRNAs are essential for the maintenance of podocyte homeostasis. Emerging evidence has demonstrated a protective role of microRNA-30a (miR-30a), a member of the miR-30 family, in podocyte injury. However, the roles of other miR-30 family members in podocyte injury are unclear. The present study was undertaken to investigate the contribution of miR-30e to the pathogenesis of podocyte injury induced by aldosterone (Aldo), as well as the underlying mechanism. After Aldo treatment, miR-30e was reduced in a dose-and time-dependent manner. Notably, overexpression of miR-30e markedly attenuated Aldo-induced apoptosis in podocytes. In agreement with this finding, miR-30e silencing led to significant podocyte apoptosis. Mitochondrial dysfunction (MtD) has been shown to be an early event in Aldo-induced podocyte injury. Here we found that overexpression of miR-30e improved Aldo-induced MtD while miR-30e silencing resulted in MtD. Next, we found that miR-30e could directly target the BCL2/adenovirus E1B-interacting protein 3-like (BNIP3L) gene. Aldo markedly enhanced BNIP3L expression in podocytes, and silencing of BNIP3L largely abolished Aldo-induced MtD and cell apoptosis. On the contrary, overexpression of BNIP3L induced MtD and apoptosis in podocytes. Together, these findings demonstrate that miR-30e protects mitochondria and podocytes from Aldo challenge by targeting BNIP3L.

Reactive oxygen species-initiated autophagy opposes aldosterone-induced podocyte injury

2016 ◽  
Vol 310 (7) ◽  
pp. F669-F678 ◽  
Author(s):  
Mi Bai ◽  
Ruochen Che ◽  
Yue Zhang ◽  
Yanggang Yuan ◽  
Chunhua Zhu ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Annexin V ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ros Generation ◽  
Dependent Manner ◽  
Related Gene ◽  
Podocyte Injury ◽  
Induced Apoptosis

Evidence has demonstrated that aldosterone (Aldo) is involved in the development and progression of chronic kidney diseases. The purpose of the present study was to investigate the role of autophagy in Aldo-induced podocyte damage and the underlying mechanism. Mouse podocytes were treated with Aldo in the presence or absence of 3-methyladenine and N-acetylcysteine. Cell apoptosis was investigated by detecting annexin V conjugates, apoptotic bodies, caspase-3 activity, and alterations of the podocyte protein nephrin. Autophagy was evaluated by measuring the expressions of light chain 3, p62, beclin-1, and autophagy-related gene 5. Aldo (10−7 mol/l) induced podocyte apoptosis, autophagy, and downregulation of nephrin protein in a time-dependent manner. Aldo-induced apoptosis was further promoted by the inhibition of autophagy via 3-methyladenine and autophagy-related gene 5 small interfering RNA pretreatment. Moreover, Aldo time dependently increased ROS generation, and H2O2 (10−4 mol/l) application remarkably elevated podocyte autophagy. After treatment with N-acetylcysteine, the autophagy induced by Aldo or H2O2 was markedly attenuated, suggesting a key role of ROS in mediating autophagy formation in podocytes. Inhibition of ROS could also lessen Aldo-induced podocyte injury. Taken together, our findings suggest that ROS-triggered autophagy played a protective role against Aldo-induced podocyte injury, and targeting autophagy in podocytes may represent a new therapeutic strategy for the treatment of podocytopathy.

scholarly journals Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

2018 ◽  
Vol 51 (3) ◽  
pp. 1364-1375 ◽  
Author(s):  
Dan Fei ◽  
Xiaona Zhang ◽  
Jinxiang Liu ◽  
Long Tan ◽  
Jie Xing ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Colony Formation ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Qrt Pcr

Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

scholarly journals Induction of MicroRNA-24 by HIF-1 Protects Against Ischemic Injury in Rat Cardiomyocytes

2012 ◽  
pp. 555-565 ◽  
Author(s):  
D.-F. LI ◽  
J. TIAN ◽  
X. GUO ◽  
L.-M. HUANG ◽  
Y. XU ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Injury ◽  
Protective Role ◽  
Luciferase Reporter ◽  
Rat Cardiomyocytes ◽  
Protein Levels ◽  
Novel Treatment ◽  
Ldh Release ◽  
Apoptosis And Necrosis

MicroRNAs are emerging as important regulators of cardiac function. This study investigated the role of microRNA-24 (miR-24) in ischemic cardiomyocytes, based on the observation that miR-24 expression was significantly enhanced in the ischemic myocardium of rats. Using primary cultured rat cardiomyocytes, cell injury was induced by ischemic conditions, and the cells were evaluated for changes in lactate dehydrogenase (LDH) release, cell viability, apoptosis and necrosis. The results showed that miR-24 was increased in myocytes exposed to ischemia. When miR-24 was further overexpressed in ischemic myocytes using the mimic RNA sequence, LDH release was reduced, cell viability was enhanced, and apoptosis and necrosis rates were both decreased. By contrast, a deficiency in miR-24 resulted in the largest LDH release, lowest cell viability and highest apoptosis and necrosis rates in normal and ischemic myocytes, with significant changes compared to that of non-transfected myocytes. Additionally, the mRNA and protein levels of the pro-apoptotic gene, BCL2L11, were down-regulated by miR-24 overexpression and up-regulated by miR-24 deficiency. The luciferase reporter assay confirmed BCL2L11 to be a target of miR-24. Overall, this study showed a protective role for miR-24 against myocardial ischemia by inhibiting BCL2L11, and may represent a potential novel treatment for ischemic heart disease.

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