MicroRNA-497-5p Functions as a Modulator of Apoptosis by Regulating Metadherin in Ovarian Cancer

Ovarian cancer (OC) has a high mortality rate among women worldwide. However, even with the advances in detection and therapeutics, the number of cases is increasing worldwide. Increasingly, microRNAs (miRNAs), including miR-497-5p, have been implicated in the progression of many cancers, but the role of miR-497-5p in OC remains unknown. The purpose of this study was to investigate the underlying molecular mechanism of miR-497-5p in OC. Herein, we find that miR-497-5p is down-regulated in OC tissues, and overexpression of miR-497-5p enhances apoptosis in OC cells. The increased apoptosis was correlated with enhanced expression of apoptosis-related proteins. MiR-497-5p directly bound the 3’-untranslated region of metadherin (MTDH), leading to the reduction of MTDH in mRNA and protein levels. Moreover, MTDH knockout promoted the apoptosis of OC cells. Taken together, we conclude that miR-497-5p contributes to cell apoptosis in OC by regulating MTDH.

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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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Mitomycin C Inhibits Esophageal Fibrosis by Regulating Cell Apoptosis and Autophagy via lncRNA-ATB and miR-200b

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.675757 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yin Zhang ◽

Qinge Wang ◽

Yuping Xu ◽

Jing Sun ◽

Yanbo Ding ◽

...

Keyword(s):

Electron Microscope ◽

Mitomycin C ◽

Cell Apoptosis ◽

Optimal Dose ◽

The Other ◽

Fibroblast Cells ◽

Transmission Electron ◽

Esophageal Strictures ◽

Related Proteins

Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.

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p53 and erbB-2 Are Not Associated in Matched Cases of Primary and Metastatic Ovarian Carcinomas

Disease Markers ◽

10.1155/2003/108643 ◽

2003 ◽

Vol 19 (1) ◽

pp. 11-17 ◽

Cited By ~ 4

Author(s):

Cristina Rodríguez-Burford ◽

David C. Chhieng ◽

Cecil R. Stockard ◽

Marc J. Kleinberg ◽

Mack N. Barnes ◽

...

Keyword(s):

Ovarian Cancer ◽

Mortality Rate ◽

Ovarian Carcinoma ◽

High Mortality ◽

Early Stage ◽

Phenotypic Expression ◽

Nuclear Accumulation ◽

Novel Therapies ◽

Ovarian Carcinomas ◽

Metastatic Lesions

Ovarian cancer has a high mortality rate largely due to the limited number of ovarian carcinomas detected at an early stage. Understanding the molecular changes occurring during the progression of ovarian carcinoma would aid in the development of therapies that may inhibit or target metastasis. Primary and metastatic lesions from 54 and 40 patients with advanced ovarian carcinoma, respectively (including matched primary and metastatic lesions from 30 patients) were evaluated for nuclear accumulation of p53 (clone BP53-12-1) and cytoplasmic and membranous immunostaining of p185 erbB-2 (clone 3B5) by immunohistochemistry. No differences in the immunostaining of p53 and p185erbB-2 (cytoplasm or membrane) were observed between primary and metastatic lesions of the matched cases. Similarly, no differences in the proportion of positive cases of p53 between primary and metastatic lesions of the matched cases was observed. Thus, novel therapies that target p53 or p185erbB-2 can utilize specimens from either primary or metastatic lesions to characterize these targets prior to therapy. Spearman correlations between p53 and p185erbB-2 (cytoplasm or membrane) immunohistochemistry scores were insignificant for the matched cases, all primary lesions, and all metastatic lesions. Also, no significant associations occurred between nuclear accumulation of p53 (positive versus negative) and phenotypic expression of p185erbB-2 (cytoplasm or membrane) immunostaining scores for the matched cases, all primary lesions, and all metastatic lesions. Thus, the nuclear accumulation of p53 and immunostaining of p185erbB-2 in the cytoplasm or on the cellular membranes are independent.

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The role of inhibins and activins in prostate cancer pathogenesis.

Endocrine Related Cancer ◽

10.1677/erc.0.0070243 ◽

2000 ◽

pp. 243-256 ◽

Cited By ~ 24

Author(s):

C R Dowling ◽

G P Risbridger

Keyword(s):

Prostate Cancer ◽

Ovarian Cancer ◽

Transforming Growth Factor Beta ◽

Transforming Growth Factor ◽

Prostate Gland ◽

Prostate Carcinogenesis ◽

Cancer Pathogenesis ◽

Number Of Patients ◽

Related Proteins

Successful prostate cancer diagnosis and management continue to provide challenges for the clinician. While interventions aimed at the containment of both early and late disease continue to fail in a significant number of patients, the search for answers must incorporate an analysis of the processes of normal and aberrant growth and development within the gland itself. Inhibin and its structurally related protein, activin, are members of the transforming-growth-factor beta (TGFbeta) superfamily. Originally identified as regulators of FSH, these proteins are now recognised to have widespread biological functions. This might be expected of proteins that are structurally homologous to TGFbeta itself, which is recognised to have regulatory roles in both normal and malignant prostate tissue. The aim of this review is to examine the relationship between inhibins, activins and their related proteins and the development of prostate cancer. The homology with TGF, the pluripotent effects of activin on various tissues and the roles for inhibins in ovarian cancer make activins and inhibins candidate growth factors for involvement at multiple sites in the progression from benign disease to cancer. In compiling this review, we aim to delineate the changes in inhibins and activins in this pathway and in doing so implicate their potential roles in the progression of carcinogenesis. We will compare the changes in inhibin and its related proteins in prostate cancer to those that are known in ovarian cancer. We will discuss the similarities and differences between the putative role of activins and TGFbeta in prostate carcinogenesis. The importance of this review lies in demonstrating that inhibin, an endocrine hormone, and its related proteins may contribute to endocrine-related cancers, such as that of the prostate gland.

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LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.631835 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yuting Zhuang ◽

Tingting Li ◽

Hongwen Xiao ◽

Jiaxu Wu ◽

Shuang Su ◽

...

Keyword(s):

Molecular Mechanism ◽

Noncoding Rna ◽

Physiological Function ◽

Luciferase Reporter ◽

Aged Mouse ◽

Progressive Decline ◽

Downstream Target ◽

Novel Target ◽

Related Proteins

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored.Methods: Senescence-associated β-galactosidases (SA-β-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism.Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-β-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence.Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

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

Cancer Cell International ◽

10.1186/s12935-020-01497-0 ◽

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.

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Fibronectin Type III Domain Containing 5 Alleviates the Inflammation and Apoptosis in Lipopolysaccharide- Induced Intestinal Epithelial Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2020.2312 ◽

2020 ◽

Vol 10 (5) ◽

pp. 669-675

Author(s):

Junzhi Pan ◽

Jie Zhang

Keyword(s):

Oxidative Stress ◽

Cell Apoptosis ◽

Intestinal Injury ◽

Intestinal Epithelial ◽

Sod Activity ◽

Fibronectin Type Iii ◽

Fibronectin Type Iii Domain ◽

Related Proteins ◽

Fibronectin Type

Intestinal injury caused by sepsis has multiple effects on the pathophysiology and development of sepsis. In this study, we aimed to explore the role of FNDC5 in progression of sepsis-induced intestinal injury. The expression of FNDC5 in blood samples of patients with sepsis-induced intestinal injury and IEC-6 cells was measured by qRT-PCR assay. Cell viability and inflammatory cytokines were evaluated by CCK-8 and ELISA assay, respectively. Oxidative stress level was detected by DCFH-DA staining and corresponding kit. Tunel assay and western blot analysis were performed to assess cell apoptosis. FNDC5 expression in patients with sepsis-induced intestinal injury was significantly decreased. The stimulation of LPS reduced expression level of FNDC5 and inhibited cell growth in IEC-6 cells. Overexpression of FNDC5 suppressed the productions of TNF-a, IL-1 , IL-6 and MCP1, diminished the level of ROS and MPO while enhanced the SOD activity. Additionally, upregulation of FNDC5 ameliorated cell apoptosis and repressed the levels of apoptosis-related proteins. FNDC5 could play a crucial role in the inflammation, oxidative stress and apoptosis in sepsis-induced intestinal injury.

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LncRNA GAS5 suppresses ovarian cancer by inducing inflammasome formation

Bioscience Reports ◽

10.1042/bsr20171150 ◽

2018 ◽

Vol 38 (2) ◽

Cited By ~ 21

Author(s):

Jie Li ◽

Chen Yang ◽

Yinguang Li ◽

Aiyue Chen ◽

Li Li ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Apoptosis ◽

Colony Formation ◽

Sandwich Elisa ◽

Ovarian Cancer Cells ◽

Cancer Tissues ◽

Lncrna Gas5

Objective: Long noncoding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is involved in various kinds of cancer. However, the role of lncGAS5 in the development of ovarian cancer remains unclear. In the present study, we explored the cellular mechanism and clinical value of lncRNA GAS5 in ovarian cancer. Methods: Quantitative real-time PCR was used to detect mRNA level of lncRNA GAS5 in 20 ovarian cancer tissues. The effect of lncRNA GAS5 on cell proliferation was performed using CCK-8 assay. Cell apoptosis was evaluated by flow cytometry. Western blotting was used to detect the protein level of lncRNA GAS5 potential target. Standard sandwich ELISA was used to quantify the level of inflammatory cytokines. The cells with stable expression of lncRNA GAS5 were injected into nude mice to study the effect of lncRNA GAS5 on tumorigenesis in vivo. Results: The expression of lncRNA GAS5 was significantly decreased in ovarian cancer tissues. Decrease in lncRNA GAS5 expression resulted in increased cell proliferation and colony formation and reduced ovarian cancer cell apoptosis. In contrast, exogenous overexpression of lncRNA GAS5 in ovarian cancer cells inhibited proliferation, colony formation, and apoptosis in ovarian cancer cells. In addition, the role of lncRNA GAS5 in ovarian cancer was associated with inflammasome formation and pyroptosis. Conclusion: These results suggested that lncRNA GAS5 acts as tumor suppressor and could be used as a potential treatment target for diagnosis and therapy of ovarian cancer.

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Parkin Modulates ERRα/eNOS Signaling Pathway in Endothelial Cells

Cellular Physiology and Biochemistry ◽

10.1159/000493713 ◽

2018 ◽

Vol 49 (5) ◽

pp. 2022-2034 ◽

Cited By ~ 4

Author(s):

Weiwei Xia ◽

Jie Yin ◽

Shuping Zhang ◽

Chuchu Guo ◽

Yuanyuan Li ◽

...

Keyword(s):

Endothelial Cells ◽

Cell Apoptosis ◽

Mitochondrial Membrane ◽

Caspase Inhibitor ◽

Experimental Setting ◽

Bafilomycin A1 ◽

Aortic Endothelial Cells ◽

Protein Levels ◽

Enos Protein

Background/Aims: Although a number of reports documented the important role of parkin in mitophagy, emerging evidence also indicated additional functions of parkin besides mitophagy. The present study was undertaken to investigate the role of parkin in the regulation of ERRα/eNOS pathway in endothelial cells (ECs). Methods: Mouse aortic endothelial cells (MAECs) and cardiac muscle HL-1 cells were transfected with parkin plasmid or siRNA. ERRα inhibitor XCT-790, autophagy inhibitor 3-MA and Bafilomycin A1, and caspase inhibitor Z-VAD-FMK were used to block autophagy or apoptosis. Western blotting was performed to examine the protein levels. Flow cytometry was applied to determine the cell apoptosis and ROS production. Mitochondrial membrane potential was measured using JC-1 and TMRM. Immunoprecipitation was performed to confirm the parkin effect on ERRα ubiquitination. Results: Overexpression of parkin resulted in a significant reduction of total-eNOS and p-eNOS in parallel with the downregulation of ERRα (a regulator of eNOS) protein and the enhancement of ERRα ubiquitination. To test the role of ERRα in regulating eNOS in this experimental setting, we treated ECs with ERRα inhibitor and found a decrement of total-eNOS and p-eNOS. On the contrary, overexpression of ERRα increased the levels of total-eNOS and p-eNOS. Meanwhile, parkin overexpression induced mitochondrial dysfunction and cell apoptosis in both ECs and HL-1 cells. Finally, we confirmed that the parkin effect on the regulation of eNOS was independent of the autophagy and apoptosis. Conclusion: These findings suggested that parkin overexpression downregulated eNOS possibly through the ubiquitination of ERRα in endothelial cells.

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Pegylated Interferon-αModulates Liver Concentrations of Activin-A and Its Related Proteins in Normal Wistar Rat

Mediators of Inflammation ◽

10.1155/2015/414207 ◽

2015 ◽

Vol 2015 ◽

pp. 1-14

Author(s):

Bassem Refaat ◽

Adel Galal El-Shemi ◽

Ahmed Mohamed Ashshi ◽

Elaf Wael Mahamid ◽

Noha Mohammed Al-Qadi

Keyword(s):

Liver Homogenate ◽

Wistar Rat ◽

Pegylated Interferon ◽

Activin A ◽

Protein Levels ◽

Male Wistar Rats ◽

Normal Rat ◽

A Subunit ◽

Related Proteins

Aims. To measure the expression of activinβA-subunit, activin IIA and IIB receptors, Smad4, Smad7, and follistatin in the liver and the liver and serum concentrations of mature activin-A and follistatin in normal rat following treatment with pegylated interferon-α(Peg-INF-α) and ribavirin (RBV).Materials and Methods. 40 male Wistar rats were divided equally into 4 groups: “control,” “Peg-only” receiving 4 injections of Peg-INF-α(6 µg/rat/week), “RBV-only” receiving ribavirin (4 mg/rat/day) orally, and “Peg & RBV” group receiving both drugs. The expression of candidate molecules in liver was measured by immunohistochemistry and quantitative PCR. The concentrations of mature proteins in serum and liver homogenate samples were measured using ELISA.Results. Peg-INF-α ± RBV altered the expression of all candidate molecules in the liver at the gene and protein levelsP<0.05and decreased activin-A and increased follistatin in serum and liver homogenates compared with the other groupsP<0.05. There were also significant correlations between serum and liver activin-A and follistatin.Conclusion. Peg-INF-αmodulates the hepatic production of activin-A and follistatin, which can be detected in serum. Further studies are needed to explore the role of Peg-INF-αon the production of activins and follistatin by the liver and immune cells.

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