scholarly journals A Comparative Transcriptome and Proteomics Study of Postpartum Ovarian Cycle Arrest in Yaks

2020 ◽  
Author(s):  
shengdong huo ◽  
Yanmei Yang ◽  
Yingpai Zhaxi ◽  
Zhou Chen ◽  
Shuyuan Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Oocyte Maturation ◽  
Ovarian Cycle ◽  
Estrogen Signaling ◽  
Cycle Arrest ◽  
Oocyte Meiosis ◽  
Gonadotrophin Releasing Hormone ◽  
Upregulated Genes ◽  
Main Factor

Abstract Background: Postpartum ovarian cycle arrest is the main factor affecting yak reproductive efficiency. There are few reports regarding the molecular regulatory mechanism of postnatal estrus on transcriptome and proteome in yaks. Our previous studies focused on the ovaries of yaks with postnatal ovarian cycle arrest and postnatal estrus yaks. In this study, RNA sequencing transcriptomic was combined with quantitative proteomic analyses to identify postpartum ovarian cycle-related genes and proteins.Results: Consequently 1,149 genes and 24 proteins were found to be up- or downregulated during postnatal estrus. The analysis of differentially regulated genes identified three gene or protein pairs that were synchronously upregulated and no gene or protein pairs that were synchronously downregulated, suggesting that these upregulated genes may regulate the postpartum ovarian cycle. The functional classification of these differentially expressed genes and proteins indicated their connection with oocyte meiosis, the estrogen signaling pathway, progesterone-mediated oocyte maturation and the gonadotrophin releasing hormone (GnRH) signaling pathway. Conclusions: In this study, a total of six genes and two proteins involved in the oocyte meiosis, the estrogen signaling pathway, progesterone-mediated oocyte maturation and the GnRH signaling pathway were identified. This is the first report of a comprehensive transcriptomic and proteomic analysis of postnatal estrus on Yaks.

Identification of Potential Genes Associated with Vemurafenib Efficacy and Melanoma Prognosis

2021 ◽  
Vol 24 ◽  
Author(s):  
Yue Qi ◽  
GuiE Ma
Keyword(s):  
Signaling Pathway ◽  
Estrogen Signaling ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Hub Genes ◽  
Ampk Signaling ◽  
Melanoma Patients ◽  
Key Genes ◽  
Neurotrophin Signaling ◽  
Upregulated Genes

Objective: This work aimed to investigate the molecular mechanisms underlying the efficacy of vemurafenib as a treatment for melanoma. Methods: The GSE52882 dataset, which includes A375 and A2058 melanoma cell lines treated with vemurafenib and dimethyl sulfoxide (DMSO), and clinical information associated with melanoma patients, were acquired from the Gene Expression Omnibus (GEO) database and University of California Santa Cruz (UCSC), respectively. Functional enrichment analysis, protein-protein interaction (PPI) network construction, sub-module analysis, and transcriptional regulation analysis were performed on overlapping differentially expressed genes (DEGs) identified in both cell lines. Finally, we performed a survival analysis based on the genes identified. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Results: A total of 447 consistently overlapping DEGs (176 up- and 271 down-regulated DEGs) were screened. Upregulated genes were enriched in pathways of neurotrophin signaling, estrogen signaling, and transcriptional misregulation in cancer. Downregulated DEGs played essential roles in melanogenesis, pathways of cancer, PI3K-Akt signaling pathway, and AMPK signaling pathway. Upregulated (MMP2, JUN, KAT28, and PIK3R3) and downregulated genes (CXCL8, CCND1, IGF1R, and ITGB3) were considered as hub genes in the PPI network. Additionally, PIK3R3 and LEF1 served as key genes in the regulatory network. The overexpression of MMP2 and CXCL8 was associated with a poor prognosis in melanoma patients. Conclusion: MMP2, CXCL8, PIK3R3, ITGB3, and LEF1 may play roles in the efficacy of vemurafenib treatment in melanoma; for example, MMP2 and PIK3R3 are likely associated with vemurafenib resistance. These findings will contribute to the development of novel therapies for melanoma.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

Involvement of the p38 MAPK signaling pathway in S-phase cell-cycle arrest induced by Furazolidone in human hepatoma G2 cells

2012 ◽  
Vol 33 (12) ◽  
pp. 1500-1505 ◽  
Author(s):  
Yu Sun ◽  
Shusheng Tang ◽  
Xi Jin ◽  
Chaoming Zhang ◽  
Wenxia Zhao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Signaling ◽  
S Phase ◽  
Mapk Signaling Pathway ◽  
Phase Cell ◽  
Human Hepatoma ◽  
Cycle Arrest

scholarly journals Ral GTPase is essential for actin dynamics and Golgi apparatus distribution in mouse oocyte maturation

Cell Division ◽  
2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ming-Hong Sun ◽  
Lin-Lin Hu ◽  
Chao-Ying Zhao ◽  
Xiang Lu ◽  
Yan-Ping Ren ◽  
...  
Keyword(s):  
Golgi Apparatus ◽  
Oocyte Maturation ◽  
Polar Body ◽  
Mouse Oocyte ◽  
Actin Dynamics ◽  
Mouse Oocytes ◽  
Oocyte Meiosis ◽  
Ral Gtpase ◽  
Polar Body Extrusion ◽  
Cytoskeleton Dynamics

Abstract Background Ral family is a member of Ras-like GTPase superfamily, which includes RalA and RalB. RalA/B play important roles in many cell biological functions, including cytoskeleton dynamics, cell division, membrane transport, gene expression and signal transduction. However, whether RalA/B involve into the mammalian oocyte meiosis is still unclear. This study aimed to explore the roles of RalA/B during mouse oocyte maturation. Results Our results showed that RalA/B expressed at all stages of oocyte maturation, and they were enriched at the spindle periphery area after meiosis resumption. The injection of RalA/B siRNAs into the oocytes significantly disturbed the polar body extrusion, indicating the essential roles of RalA/B for oocyte maturation. We observed that in the RalA/B knockdown oocytes the actin filament fluorescence intensity was significantly increased at the both cortex and cytoplasm, and the chromosomes were failed to locate near the cortex, indicating that RalA/B regulate actin dynamics for spindle migration in mouse oocytes. Moreover, we also found that the Golgi apparatus distribution at the spindle periphery was disturbed after RalA/B depletion. Conclusions In summary, our results indicated that RalA/B affect actin dynamics for chromosome positioning and Golgi apparatus distribution in mouse oocytes.

scholarly journals Expression Profile and Prognostic Value of Wnt Signaling Pathway Molecules in Colorectal Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1331
Author(s):  
Yung-Fu Wu ◽  
Chih-Yang Wang ◽  
Wan-Chun Tang ◽  
Yu-Cheng Lee ◽  
Hoang Dang Khoa Ta ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Mrna Levels ◽  
Key Factor ◽  
Canonical Wnt ◽  
Upregulated Genes

Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (DPEP1, KRT80, FABP6, NKD2, FOXQ1, CEMIP, ETV4, TESC, FUT1, and GAS2) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify NKD2, FOXQ1, and CEMIP as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.

scholarly journals The PI3K Inhibitor XH30 Enhances Response to Temozolomide in Drug-Resistant Glioblastoma via the Noncanonical Hedgehog Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Ji ◽  
Zhihui Zhang ◽  
Songwen Lin ◽  
Chunyang Wang ◽  
Jing Jin ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hedgehog Signaling ◽  
Kinase Inhibitor ◽  
Therapeutic Option ◽  
Hedgehog Signaling Pathway ◽  
Orthotopic Mouse Model ◽  
Cycle Arrest ◽  
The Central Nervous System

Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system. Temozolomide (TMZ)–based adjuvant treatment has improved overall survival, but clinical outcomes remain poor; TMZ resistance is one of the main reasons for this. Here, we report a new phosphatidylinositide 3-kinase inhibitor, XH30; this study aimed to assess the antitumor activity of this compound against TMZ-resistant GBM. XH30 inhibited cell proliferation in TMZ-resistant GBM cells (U251/TMZ and T98G) and induced cell cycle arrest in the G1 phase. In an orthotopic mouse model, XH30 suppressed TMZ-resistant tumor growth. XH30 was also shown to enhance TMZ cytotoxicity both in vitro and in vivo. Mechanistically, the synergistic effect of XH30 may be attributed to its repression of the key transcription factor GLI1 via the noncanonical hedgehog signaling pathway. XH30 reversed sonic hedgehog–triggered GLI1 activation and decreased GLI1 activation by insulin-like growth factor 1 via the noncanonical hedgehog signaling pathway. These results indicate that XH30 may represent a novel therapeutic option for TMZ-resistant GBM.

scholarly journals Transcriptomic Alterations Induced by Vemurafenib After Treatment of Melanoma: A Comprehensive Bioinformatics Analysis

2021 ◽  
Author(s):  
Jiaheng Xie ◽  
Yuan Cao ◽  
Zhechen Zhu ◽  
Shujie Ruan ◽  
Ming Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Enrichment Analysis ◽  
Skin Cell ◽  
Cycle Arrest ◽  
Go Enrichment ◽  
Cellular Sensitivity ◽  
Clinical Benefits ◽  
Melanoma Treatment ◽  
Upregulated Genes

Abstract Backgrounds Melanoma is a highly aggressive kind of cancer with very poor prognosis. B-raf inhibitor vemurafenib has indeed harvested substantial clinical benefits. Nevertheless, its drug resistance has also hampered scientists effort towards successful melanoma treatment. In this study, we used data derived from the GEO database to analyze the effect on vemurafenib sensitive cell lines after vemurafenib treatment. GEO datasets GSE42872 (cohort1), GSE127988 (cohort2), GSE110054 (cohort3) were included in the analysis. Results We found 25 common Differentially Expressed Genes(DEGs) in 3 datasets, including 10 upregulated genes and 15 downregulated genes after vemurefenib application. Analysis using web tool TIMER showed significant correlation of the upregulated genes with immune infiltration level in skin cell melanoma. GO enrichment analysis showed that after vemurafenib treatment, all datasets showed downregulation in DNA replication and cell cycle arrest. Meanwhile, genes related to neuro-generation, extracellular matrix and cell-cell adhesion were significantly enriched in all three datasets. KEGG analysis showed that pathways like P53, PI3K-Akt, and Rap signaling pathways were enriched in DEGs after vemurafenib administration.Conlusions The findings of the candidate DEGs and pathways may not only reveal the cellular sensitivity to vemurafenib treatment, but also give rise to a better understanding of the mechanism of cancer cell cycle arrest and cellular resistance towards vemurafenib targeted therapy.

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