scholarly journals MALAT1 Activates the P53 Signaling Pathway by Regulating MDM2 to Promote Ischemic Stroke

2018 ◽  
Vol 50 (6) ◽  
pp. 2216-2228 ◽  
Author(s):  
Ting Zhang ◽  
Hongmei Wang ◽  
Qiang Li ◽  
Jianliang Fu ◽  
Jiankang Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Bioinformatics Analysis ◽  
Mrna Levels ◽  
P53 Pathway ◽  
P53 Signaling ◽  
Related Proteins ◽  
P53 Signaling Pathway

Background/Aims: This study focused on evaluating the effect of MALAT1 and MDM2 on ischemic stroke through regulation of the p53 signaling pathway. Materials: Bioinformatics analysis was performed to identify abnormally expressed lncRNAs, mRNAs and their associated pathways. Oxygen-glucose deprivation/reoxygenation (OGD/R) in cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in mice were performed to simulate an ischemic stroke environment. Western blot and qRT-PCR were used to examine lncRNA expression and mRNA levels. Fluorescence in situ hybridization (FISH) LncRNA was used to locate mRNA. MTT and flow cytometry were performed to examine cell proliferation and apoptosis. Finally, immunohistochemistry was used to observe the expression of genes in vivo. Results: MALAT1 and MDM2, which exhibit strong expression in stroke tissues, were subjected to bioinformatics analysis, and the p53 pathway was chosen for further study. MALAT1, MDM2 and p53 signaling pathway-related proteins were all up regulated in OGD/R cells. Furthermore, Malat1, Mdm2 and p53 pathway related-proteins were also up regulated in MCAO/R mice. Both MALAT1 and MDM2 were localized in the nuclei. Down regulation of MALAT1 and MDM2 enhanced cell proliferation ability and reduced apoptosis, resulting in decreased infarct size in MCAO/R brains. Conclusion: These results indicate that MALAT1/MDM2/p53 signaling pathway axis may provide more effective clinical therapeutic strategy for patients with ischemic stroke.

scholarly journals Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Shui Liu ◽  
Xiaoxiao Yao ◽  
Dan Zhang ◽  
Jiyao Sheng ◽  
Xin Wen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Gene Network ◽  
Bioinformatics Analysis ◽  
Expression Profiles ◽  
Mrna Levels ◽  
Qrt Pcr ◽  
P53 Signaling ◽  
Tf Gene ◽  
P53 Signaling Pathway

Hepatocellular carcinoma (HCC) accounts for a significant proportion of liver cancer, which has become the second most common cause of cancer-related mortality worldwide. To investigate the potential mechanisms of invasion and progression of HCC, bioinformatics analysis and validation by qRT-PCR were performed. We found 237 differentially expressed genes (DEGs) including EGR1, FOS, and FOSB, which were three cancer-related transcription factors. Subsequently, we constructed TF-gene network and miRNA-TF-mRNA network based on data obtained from mRNA and miRNA expression profiles for analysis of HCC. We found that 42 key genes from the TF-gene network including EGR1, FOS, and FOSB were most enriched in the p53 signaling pathway. The qRT-PCR data confirmed that mRNA levels of EGR1, FOS, and FOSB all were decreased in HCC tissues. In addition, we confirmed that the mRNA levels of CCNB1, CCNB2, and CHEK1, three key markers of the p53 signaling pathway, were all increased in HCC tissues by bioinformatics analysis and qRT-PCR validation. Therefore, we speculated that miR-181a-5p, which was upregulated in HCC tissues, could regulate FOS and EGR1 to promote the invasion and progression of HCC by p53 signaling pathway. Overall, the study provides support for the possible mechanisms of progression in HCC.

SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway

2020 ◽  
Author(s):  
Yuanji Xu ◽  
Kunshou Zhu ◽  
Junqiang Chen ◽  
Liyan Lin ◽  
Zhengrong Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Squamous Carcinoma ◽  
Tumor Formation ◽  
Squamous Carcinoma Cells ◽  
P53 Signaling ◽  
P53 Signaling Pathway

Abstract SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

scholarly journals Angiotensin II AT2 receptor regulates ureteric bud morphogenesis

2010 ◽  
Vol 298 (3) ◽  
pp. F807-F817 ◽  
Author(s):  
Renfang Song ◽  
Melissa Spera ◽  
Colleen Garrett ◽  
Samir S. El-Dahr ◽  
Ihor V. Yosypiv
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Ex Vivo ◽  
Branching Morphogenesis ◽  
Mrna Levels ◽  
Ureteric Bud ◽  
Embryonic Mouse ◽  
Genetic Inactivation ◽  
The Impact

ANG II AT2 receptor (AT2R)-deficient mice exhibit abnormal ureteric bud (UB) budding, increased incidence of double ureters, and vesicoureteral reflux. However, the role of the AT2R during UB morphogenesis and the mechanisms by which aberrant AT2R signaling disrupts renal collecting system development have not been fully defined. In this study, we mapped the expression of the AT2R during mouse metanephric development, examined the impact of disrupted AT2R signaling on UB branching, cell proliferation, and survival, and investigated the cross talk of the AT2R with the glial-derived neurotrophic factor ( GDNF)/ c-Ret/Wnt11 signaling pathway. Embryonic mouse kidneys express AT2R in the branching UB and the mesenchyme. Treatment of embryonic day 12.5 ( E12.5) metanephroi with the AT2R antagonist PD123319 or genetic inactivation of the AT2R in mice inhibits UB branching, decreasing the number of UB tips compared with control (34 ± 1.0 vs. 43 ± 0.6, P < 0.01; 36 ± 1.8 vs. 48 ± 1.3, P < 0.01, respectively). In contrast, treatment of metanephroi with the AT2R agonist CGP42112 increases the number of UB tips compared with control (48 ± 1.8 vs. 39 ± 12.3, P < 0.05). Using real-time quantitative RT-PCR and whole mount in situ hybridization, we demonstrate that PD123319 downregulates the expression of GDNF, c-Ret, Wnt11, and Spry1 mRNA levels in E12.5 metanephroi grown ex vivo. AT2R blockade or genetic inactivation of AT2R stimulates apoptosis and inhibits proliferation of the UB cells in vivo. We conclude that AT2R performs essential functions during UB branching morphogenesis via control of the GDNF/c-Ret/Wnt11 signaling pathway, UB cell proliferation, and survival.

scholarly journals RIOK2 Inhibitor NSC139021 Exerts Anti-Tumor Effects on Glioblastoma via Inducing Skp2-Mediated Cell Cycle Arrest and Apoptosis

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1244
Author(s):  
Min Yu ◽  
Xiaoyan Hu ◽  
Jingyu Yan ◽  
Ying Wang ◽  
Fei Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Cyclin E ◽  
Intraperitoneal Administration ◽  
Glioblastoma Cells ◽  
P53 Signaling ◽  
Cycle Arrest ◽  
P53 Signaling Pathway

Up to now, the chemotherapy approaches for glioblastoma were limited. 1-[2-Thiazolylazo]-2-naphthol (named as NSC139021) was shown to significantly inhibit the proliferation of prostate cancer cells by targeting the atypical protein kinase RIOK2. It is documented that RIOK2 overexpressed in glioblastoma. However, whether NSC139021 can inhibit the growth of glioblastoma cells and be a potential drug for glioblastoma treatment need to be clarified. In this study, we investigated the effects of NSC139021 on human U118MG, LN-18, and mouse GL261 glioblastoma cells and the mouse models of glioblastoma. We verified that NSC139021 effectively inhibited glioblastoma cells proliferation, but it is independent of RIOK2. Our data showed that NSC139021 induced cell cycle arrest at G0/G1 phase via the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway in G1/S checkpoint regulation. In addition, NSC139021 also increased the apoptosis of glioblastoma cells by activating the p53 signaling pathway and increasing the levels of Bax and cleaved caspase 3. Furthermore, intraperitoneal administration of 150 mg/kg NSC139021 significantly suppressed the growth of human and mouse glioblastoma in vivo. Our study suggests that NSC139021 may be a potential chemotherapy drug for the treatment of glioblastoma by targeting the Skp2-p27/p21-Cyclin E/CDK2-pRb signaling pathway.

scholarly journals PPM1D Knockdown Suppresses Cell Proliferation, Promotes Cell Apoptosis, and Activates p38 MAPK/p53 Signaling Pathway in Acute Myeloid Leukemia

2020 ◽  
Vol 19 ◽  
pp. 153303382094231
Author(s):  
Bin Li ◽  
Jie Hu ◽  
Di He ◽  
Qi Chen ◽  
Suna Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Protein Phosphatase ◽  
Cell Apoptosis ◽  
Myeloid Leukemia ◽  
P53 Signaling ◽  
P53 Signaling Pathway ◽  
Acute Myeloid

Objectives: This study was to explore the effect of protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown on proliferation and apoptosis as well as p38 MAPK/p53 signaling pathway in acute myeloid leukemia. Methods: The expression of protein phosphatase, Mg2+/Mn2+ dependent 1D was detected in acute myeloid leukemia cell lines including SKM-1, KG-1, AML-193, and THP-1 cells, and normal bone marrow mononuclear cells isolated from healthy donors. The knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D was conducted by transfecting small interfering RNA into AML-193 cells and KG-1 cells. Results: The relative messenger RNA/protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were higher in SKM-1, KG-1, AML-193, and THP-1 cells compared with control cells (normal bone marrow mononuclear cells). After transfecting protein phosphatase, Mg2+/Mn2+ dependent 1D small interfering RNA into AML-193 cells and KG-1 cells, both messenger RNA and protein expressions of protein phosphatase, Mg2+/Mn2+ dependent 1D were significantly reduced, indicating the successful transfection. Most importantly, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D suppressed cell proliferation and promoted cell apoptosis in AML-193 cells and KG-1 cells. In addition, knockdown of protein phosphatase, Mg2+/Mn2+ dependent 1D enhanced the expressions of p-p38 and p53 in AML-193 cells and KG-1 cells. The above observation suggested that protein phosphatase, Mg2+/Mn2+ dependent 1D knockdown suppressed cell proliferation, promoted cell apoptosis, and activated p38 MAPK/p53 signaling pathway in acute myeloid leukemia cells. Conclusion: Protein phosphatase, Mg2+/Mn2+ dependent 1D is implicated in acute myeloid leukemia carcinogenesis, which illuminates its potential role as a treatment target for acute myeloid leukemia.

scholarly journals Mir10a aggravates the ischemia-reperfusion kidney injury by inhibiting the PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Dongsheng Xu ◽  
Wenjun Li ◽  
Tao Zhang ◽  
Gang Wang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Rt Pcr ◽  
Apoptosis Rate ◽  
Related Proteins

Abstract Background To investigate the effect of miR-10a on PI3K/AKT signaling pathway. The ischemia-reperfusion injury models of rats were simulated in vivo . Methods RT-PCR was used to test the expression of miR-10a. The serum creatinine and urea nitrogen levels were determined. The pathological changes and the apoptosis of renal cells were observed. The model of HK-2 cells with hypoxia-reoxygenation was established in vitro. The cell proliferation and apoptosis rate were tested by CCK8, clone formation and flow cytometry, respectively. The apoptosis-related proteins and PIK3CA and PI3K/AKT signaling pathway-related proteins were detected by Western blot both in vivo and intro . The dual luciferase assay was used to verify whether PIK3CA is a target gene of miR-10a. PIK3CA gene was over-expression or silenced. The transfection efficiency was verified by RT-PCR and the above experiments were repeated. Results Compared with I/R group, miR-10a RNA was significantly increased in renal tissue of miR-10a group, serum Cr and BUN levels, and renal injury score and apoptosis index were significantly increased, while the expression of PI3K/AKT signaling pathway-related proteins were significantly inhibited. However, the indicators above were contrary in anti-miR group. In comparison with H/R group, miR-10a RNA expression was remarkably increased in miR-10a cells and the cell proliferation was inhibited. The apoptosis rate was increased and the expression of PI3K/AKT signaling pathway-related proteins were down-regulated. However, the indicators above were contrary in anti-miR group. Conclusion miR-10a can aggravate the ischemia-reperfusion-induced renal injury in rats by targeting PIK3CA and inhibitingPI3K/AKT signaling pathway.

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