scholarly journals The Recurrent Mutation in PATL2 Inhibits Its Degradation Thus Causing Female Infertility Characterized by Oocyte Maturation Defect Through Regulation of the Mos-MAPK Pathway

2021 ◽  
Vol 9 ◽  
Author(s):  
Qiqi Cao ◽  
Chun Zhao ◽  
Congjing Wang ◽  
Lingbo Cai ◽  
Meng Xia ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Oocyte Maturation ◽  
Translational Regulation ◽  
Rna Binding ◽  
Polar Body ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Female Infertility ◽  
Meiotic Maturation ◽  
Recurrent Mutations

PAT1 homolog 2 (PATL2), encoding an RNA-binding protein, is a repressor involved in the translational regulation of maternal mRNAs during oocyte maturation. Previous studies have reported mutations in PATL2 those led to female infertility with oocyte maturation arrest; however, the mechanisms by which mutations affected meiotic maturation remained unclear. Here, we identified several novel and recurrent mutations of PATL2 in patients with similar phenotype, and chose the missense mutation c.649 T>A p.Tyr217Asn in PATL2 (PATL2Y217N) as a typical to investigate the underlying mechanisms. We confirmed that this mutation disturbed oocyte maturation and observed morphological defects of large polar body, symmetrical division and abnormal spindle after microinjection of corresponding mutated mRNA. We further evaluated the effect of the PATL2Y217N mutation in 293T cells, and found this mutation decreased the ubiquitination level and degradation of PATL2. Then, abnormally increased PATL2 bound mRNAs of Mos, an upstream activator of mitogen activated protein kinase (MAPK), to regulate its translational activity and subsequently impaired MAPK signaling pathway and oocyte meiosis. These results dissented from the previous view that PATL2 mutations reduced their expression and highlight the role of PATL2 in translational regulation of Mos and its association with MAPK signaling pathway during oocyte meiotic maturation.

scholarly journals RNA-binding protein QKI suppresses breast cancer via RASA1/MAPK signaling pathway

2021 ◽  
Vol 9 (2) ◽  
pp. 104-104
Author(s):  
Yun Cao ◽  
Chengyu Chu ◽  
Xiaoyan Li ◽  
Siwen Gu ◽  
Qiang Zou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Heat shock protein 90α couples with the MAPK-signaling pathway to determine meiotic maturation of porcine oocytes1

2018 ◽  
Vol 96 (8) ◽  
pp. 3358-3369 ◽  
Author(s):  
Yun-Hua Liu ◽  
Xiao-Man Liu ◽  
Pei-Chao Wang ◽  
Xiao-Xia Yu ◽  
Jia-Kun Miao ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Meiotic Maturation

scholarly journals A long noncoding RNA binding to QKI-5 regulates germ cell apoptosis via p38 MAPK signaling pathway

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Kai Li ◽  
Shunshun Zhong ◽  
Yanyun Luo ◽  
Dingfeng Zou ◽  
Mengzhen Li ◽  
...  
Keyword(s):  
Germ Cell ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Cell Apoptosis ◽  
Rna Binding ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Germline Development ◽  
Germ Cell Apoptosis ◽  
Male Germline

Abstract Spermatogenesis is the complex process of male germline development and requires coordinated interactions by multiple gene products that undergo strict developmental regulations. Increasing evidence has suggested that a number of long noncoding RNAs (lncRNAs) may function as important regulatory molecules in various physiological and pathological processes by binding to specific proteins. Here, we identified a subset of QKI-5-binding lncRNAs in the mouse testis through the integrated analyses of RNA immunoprecipitation (RIP)-microarray and biological verification. Among the lncRNAs, we revealed that NONMMUT074098.2 (Lnc10), which was highly expressed in the spermatogonia and spermatocytes of the testis, interacted with QKI-5. Furthermore, Lnc10 depletion promoted germ cell apoptosis via the activation of p38 MAPK, whereas the simultaneous knockdown of QKI-5 could rescue the apoptotic phenotype and the activation of p38 MAPK, which were induced by the loss of Lnc10. These data indicated that the Lnc10-QKI-5 interaction was associated with the regulatory roles of QKI-5 and that the Lnc10-QKI-5 interaction inhibited the regulation of QKI-5 on the downstream p38 MAPK signaling pathway. Additionally, we functionally characterized the biological roles of Lnc10 and found that the knockdown of Lnc10 promoted the apoptosis of spermatogenic cells in vivo; this suggested that Lnc10 had an important biological role in mouse spermatogenesis. Thus, our study provides a potential strategy to investigate the biological significance of lncRNA-RBP interactions during male germline development.

scholarly journals PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

2021 ◽  
Author(s):  
Zhiqiang Han ◽  
Dongming Liu ◽  
Lu Chen ◽  
Yuchao He ◽  
Xiangdong Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Rna Seq ◽  
Hcc Cells

Abstract Background Some studies have reported that the activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1, as a critical ribosome has been rarely reported in human tumors. Thus, the roles of PNO1 in HCC should be explored. Methods We collected 150 formalin-fixed and paraffin-embedded (FFPE) samples and 8 fresh samples to explore the expression and prognosis of PNO1 in HCC by immunohistochemistry, Western Blotting and RT-PCR. Public databases (TCGA and GEO) were used to verify the expression and prognosis. The functions of PNO1 in HCC was verified by in vitro and in vivo experiments. The underlying molecular mechanisms of PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results PNO1 expression was considerably higher in HCC tissues and the higher expression of PNO1 was associated with poor prognosis of HCC patients. In vitro experiments indicated that PNO1 overexpression promoted proliferation and depressed apoptosis of HCC cells. In addition, high expression of PNO1 increased autophagy of HCC cells. Consistent results were also observed in vivo experiments. The results of the RNA-seq analysis indicted that PNO1 as an oncogene promoted HCC progression through the MAPK signaling pathway. The results were also verified by in vivo experiments. Conclusions PNO1 was overexpressed in HCC, promoted autophagy and inhibited apoptosis of HCC cells via the MAPK signaling pathway.

scholarly journals PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zhiqiang Han ◽  
Dongming Liu ◽  
Lu Chen ◽  
Yuchao He ◽  
Xiangdong Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Malignant Tumors ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Hcc Cells

AbstractSome studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

scholarly journals STAMBP promotes lung adenocarcinoma metastasis by regulating the EGFR/MAPK signaling pathway

Neoplasia ◽  
2021 ◽  
Vol 23 (6) ◽  
pp. 607-623
Author(s):  
Hui Xu ◽  
Xiaomei Yang ◽  
Xiaofeng Xuan ◽  
Di Wu ◽  
Jieru Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

Caffeine suppresses the progression of human glioblastoma via cathepsin B and MAPK signaling pathway

2016 ◽  
Vol 33 ◽  
pp. 63-72 ◽  
Author(s):  
Yu-Chen Cheng ◽  
You-Ming Ding ◽  
Dueng-Yuan Hueng ◽  
Jang-Yi Chen ◽  
Ying Chen
Keyword(s):  
Signaling Pathway ◽  
Cathepsin B ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Human Glioblastoma
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