scholarly journals In Vitro CSC-derived Cardiomyocytes Exhibit the Typical microRNA-mRNA Blueprint of Endogenous Cardiomyocytes

2021 ◽  
Author(s):  
Mariangela Scalise ◽  
Fabiola Marino ◽  
Luca Salerno ◽  
Mancuso Teresa ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Regulators ◽  
Cardiomyocyte Differentiation ◽  
Down Regulation ◽  
Stem Cell Expansion ◽  
Cell Cycle Genes ◽  
Neonatal Cardiomyocytes ◽  
Gene Regulatory ◽  
Regulation Of Cell Cycle

Abstract miRNAs modulate cardiomyocyte specification in embryonic hearts and in pluripotent stem cells by targeting mRNAs of cell cycle regulators and acting in gene regulatory loops that complete commitment to the cardiac muscle lineage. It is still unknown if/to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). RNASeq comparison of “CSCs vs. iCMs” mRNome and microRNome showed a balanced up-regulation of sarcomere and mitochondrial related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs did not reach the levels of mouse terminally differentiated adult cardiomyocytes (aCMs), while they get to intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs while those miRs positively regulating stem cell expansion and self-renewal were down-regulated. The specific networks of miRNA/mRNAs operative in iCMs closely resembled miRNA/mRNA networks of aCMs. Two of these miRs, miR-1 and miR-499, enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of aCMs.

scholarly journals In vitro CSC-derived cardiomyocytes exhibit the typical microRNA-mRNA blueprint of endogenous cardiomyocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mariangela Scalise ◽  
Fabiola Marino ◽  
Luca Salerno ◽  
Teresa Mancuso ◽  
Donato Cappetta ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Terminal Differentiation ◽  
Cell Cycle Regulators ◽  
Cardiomyocyte Differentiation ◽  
Down Regulation ◽  
Cell Cycle Genes ◽  
Neonatal Cardiomyocytes ◽  
Gene Regulatory ◽  
Regulation Of Cell Cycle

AbstractmiRNAs modulate cardiomyocyte specification by targeting mRNAs of cell cycle regulators and acting in cardiac muscle lineage gene regulatory loops. It is unknown if or to-what-extent these miRNA/mRNA networks are operative during cardiomyocyte differentiation of adult cardiac stem/progenitor cells (CSCs). Clonally-derived mouse CSCs differentiated into contracting cardiomyocytes in vitro (iCMs). Comparison of “CSCs vs. iCMs” mRNome and microRNome showed a balanced up-regulation of CM-related mRNAs together with a down-regulation of cell cycle and DNA replication mRNAs. The down-regulation of cell cycle genes and the up-regulation of the mature myofilament genes in iCMs reached intermediate levels between those of fetal and neonatal cardiomyocytes. Cardiomyo-miRs were up-regulated in iCMs. The specific networks of miRNA/mRNAs operative in iCMs closely resembled those of adult CMs (aCMs). miR-1 and miR-499 enhanced myogenic commitment toward terminal differentiation of iCMs. In conclusions, CSC specification/differentiation into contracting iCMs follows known cardiomyo-MiR-dependent developmental cardiomyocyte differentiation trajectories and iCMs transcriptome/miRNome resembles that of CMs.

scholarly journals Upregulation of cell cycle genes in head and neck cancer patients may be antagonized by erufosine’s down regulation of cell cycle processes in OSCC cells

Oncotarget ◽  
2017 ◽  
Vol 9 (5) ◽  
pp. 5797-5810 ◽  
Author(s):  
Shariq S. Ansari ◽  
Ashwini K. Sharma ◽  
Michael Zepp ◽  
Elizabet Ivanova ◽  
Frank Bergmann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Head And Neck Cancer ◽  
Head And Neck ◽  
Cancer Patients ◽  
Neck Cancer ◽  
Down Regulation ◽  
Cell Cycle Genes ◽  
Regulation Of Cell Cycle

Anti-glioma Efficacy and Mechanism of Action of Tripolinolate A from Tripolium pannonicum

Planta Medica ◽  
2018 ◽  
Vol 84 (11) ◽  
pp. 786-794
Author(s):  
Weiyun Chai ◽  
Lu Chen ◽  
Xiao-Yuan Lian ◽  
Zhizhen Zhang
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Cell Cycle Regulators ◽  
Expression Levels ◽  
Multiple Tumor ◽  
Glioma Growth

AbstractTripolinolate A as a new bioactive phenolic ester was previously isolated from a halophyte of Tripolium pannonicum. However, the in vitro and in vivo anti-glioma effects and mechanism of tripolinolate A have not been investigated. This study has demonstrated that (1) tripolinolate A inhibited the proliferation of different glioma cells with IC50 values of 7.97 to 14.02 µM and had a significant inhibitory effect on the glioma growth in U87MG xenograft nude mice, (2) tripolinolate A induced apoptosis in glioma cells by downregulating the expressions of antiapoptotic proteins and arrested glioma cell cycle at the G2/M phase by reducing the expression levels of cell cycle regulators, and (3) tripolinolate A also remarkably reduced the expression levels of several glioma metabolic enzymes and transcription factors. All data together suggested that tripolinolate A had significant in vitro and in vivo anti-glioma effects and the regulation of multiple tumor-related regulators and transcription factors might be responsible for the activities of tripolinolate A against glioma.

scholarly journals Functions of Cyclin A1 in the Cell Cycle and Its Interactions with Transcription Factor E2F-1 and the Rb Family of Proteins

1999 ◽  
Vol 19 (3) ◽  
pp. 2400-2407 ◽  
Author(s):  
Rong Yang ◽  
Carsten Müller ◽  
Vong Huynh ◽  
Yuen K. Fung ◽  
Amy S. Yee ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Mitotic Cell ◽  
Histone H1 ◽  
Mitotic Cell Cycle ◽  
Osteosarcoma Cell ◽  
Cell Cycle Regulators ◽  
Cyclin A1 ◽  
Transcription Factor E2f

ABSTRACT Human cyclin A1, a newly discovered cyclin, is expressed in testis and is thought to function in the meiotic cell cycle. Here, we show that the expression of human cyclin A1 and cyclin A1-associated kinase activities was regulated during the mitotic cell cycle. In the osteosarcoma cell line MG63, cyclin A1 mRNA and protein were present at very low levels in cells at the G0 phase. They increased during the progression of the cell cycle and reached the highest levels in the S and G2/M phases. Furthermore, the cyclin A1-associated histone H1 kinase activity peaked at the G2/M phase. We report that cyclin A1 could bind to important cell cycle regulators: the Rb family of proteins, the transcription factor E2F-1, and the p21 family of proteins. The in vitro interaction of cyclin A1 with E2F-1 was greatly enhanced when cyclin A1 was complexed with CDK2. Associations of cyclin A1 with Rb and E2F-1 were observed in vivo in several cell lines. When cyclin A1 was coexpressed with CDK2 in sf9 insect cells, the CDK2-cyclin A1 complex had kinase activities for histone H1, E2F-1, and the Rb family of proteins. Our results suggest that the Rb family of proteins and E2F-1 may be important targets for phosphorylation by the cyclin A1-associated kinase. Cyclin A1 may function in the mitotic cell cycle in certain cells.

scholarly journals Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma

2018 ◽  
Vol 115 (37) ◽  
pp. 9282-9287 ◽  
Author(s):  
Roland Sonntag ◽  
Nives Giebeler ◽  
Yulia A. Nevzorova ◽  
Jörg-Martin Bangen ◽  
Dirk Fahrenkamp ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Gene Signature ◽  
Cyclin Dependent Kinase ◽  
Regulatory Subunits ◽  
Cyclin E1 ◽  
Quiescent Cells ◽  
Similar Expression Profile ◽  
Regulation Of Cell Cycle

E-type cyclins E1 (CcnE1) and E2 (CcnE2) are regulatory subunits of cyclin-dependent kinase 2 (Cdk2) and thought to control the transition of quiescent cells into the cell cycle. Initial findings indicated that CcnE1 and CcnE2 have largely overlapping functions for cancer development in several tumor entities including hepatocellular carcinoma (HCC). In the present study, we dissected the differential contributions of CcnE1, CcnE2, and Cdk2 for initiation and progression of HCC in mice and patients. To this end, we tested the HCC susceptibility in mice with constitutive deficiency for CcnE1 or CcnE2 as well as in mice lacking Cdk2 in hepatocytes. Genetic inactivation of CcnE1 largely prevented development of liver cancer in mice in two established HCC models, while ablation of CcnE2 had no effect on hepatocarcinogenesis. Importantly, CcnE1-driven HCC initiation was dependent on Cdk2. However, isolated primary hepatoma cells typically acquired independence on CcnE1 and Cdk2 with increasing progression in vitro, which was associated with a gene signature involving secondary induction of CcnE2 and up-regulation of cell cycle and DNA repair pathways. Importantly, a similar expression profile was also found in HCC patients with elevated CcnE2 expression and poor survival. In general, overall survival in HCC patients was synergistically affected by expression of CcnE1 and CcnE2, but not through Cdk2. Our study suggests that HCC initiation specifically depends on CcnE1 and Cdk2, while HCC progression requires expression of any E-cyclin, but no Cdk2.

Stage specific expression of cell cycle genes during in vivo or in vitro development of ovarian follicles in sheep

2016 ◽  
Vol 143 ◽  
pp. 1-7 ◽  
Author(s):  
V. Praveen Chakravarthi ◽  
S.S.R. Kona ◽  
A.V.N. Siva Kumar ◽  
M. Bhaskara ◽  
V.H. Rao
Keyword(s):  
Cell Cycle ◽  
Ovarian Follicles ◽  
Specific Expression ◽  
In Vitro Development ◽  
Cell Cycle Genes ◽  
Vitro Development

The Cdk and PCNA domains on p21Cip1 both function to inhibit G1/S progression during hyperoxia

2004 ◽  
Vol 286 (3) ◽  
pp. L506-L513 ◽  
Author(s):  
Christopher E. Helt ◽  
Rhonda J. Staversky ◽  
Yi-Jang Lee ◽  
Robert A. Bambara ◽  
Peter C. Keng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Fluorescent Protein ◽  
Nuclear Antigen ◽  
Cell Cycle Regulators ◽  
Amino Terminal ◽  
Binding Domains ◽  
Green Fluorescent

This study investigates molecular mechanisms underlying cell cycle arrest when cells are exposed to high levels of oxygen (hyperoxia). Hyperoxia has previously been shown to increase expression of the cell cycle regulators p53 and p21. In the current study, we found that p53-deficient human lung adenocarcinoma H1299 cells failed to induce p21 or growth arrest in G1 when exposed to 95% oxygen. Instead, cells arrested in S and G2. Stable expression of p53 restored induction of p21 and G1 arrest without affecting mRNA expression of the other Cip or INK4 G1 kinase inhibitors. To confirm the role of p21 in G1 arrest, we created H1299 cells with tetracycline-inducible expression of enhanced green fluorescent protein (EGFP), EGFP fused to p21 (EGFp21), or EGFP fused to p27 (EGFp27), a related cell cycle inhibitor. The amino terminus of p21 and p27 bind cyclin-dependent kinases (Cdk), whereas the carboxy terminus of p21 binds the sliding clamp proliferating cell nuclear antigen (PCNA). EGFp21 or EGFp27, but not EGFP by itself, restored G1 arrest during hyperoxia. When separately overexpressed, the amino-terminal Cdk and carboxy-terminal PCNA binding domains of p21 each prevented cells from exiting G1 during exposure. These findings demonstrate that exposure in vitro to hyperoxia exerts G1 arrest through p53-dependent induction of p21 that suppresses Cdk and PCNA activity. Because PCNA also participates in DNA repair, these results raise the possibility that p21 also affects repair of oxidized DNA.

scholarly journals PBF, a proto-oncogene in esophageal carcinoma

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 748-756
Author(s):  
Shi-hai Lian ◽  
Jun-ding Song ◽  
Yi Huang
Keyword(s):  
Cell Cycle ◽  
Esophageal Carcinoma ◽  
Cell Function ◽  
Function Analysis ◽  
Cell Phenotype ◽  
Down Regulation ◽  
Apoptosis Pathway ◽  
Related Cell ◽  
Rnai Technology

AbstractEmerging evidence shows that the pituitary tumour-transforming gene (PTTG)-binding factor (PBF) functions as a proto-oncogene in some tumors. However, the precise functions of PBF in tumorigenesis and its action mechanisms remain largely unknown. Here for the first time we demonstrated that PBF was associated with a tumor-related cell phenotype in esophageal carcinoma (ESCA) and identified the involved signaling pathways. PBF was up-regulated in ESCA tissues (Data from GEPIA) and cells. Then we down-regulated PBF in ESCA cell lines, Eca-109 and TE-1, by using RNAi technology. Cell function analysis suggested that down-regulation of PBF could inhibit tumor-related cell phenotypes, including proliferation, motility, apoptosis and cell cycle, in Eca-109 and TE-1 cells. Mechanism investigation suggested that apoptosis induced by PBF knockdown may be mediated by the activation of the mitochondrial apoptosis pathway and cell cycle arrest. AKT/mTOR and Wnt3a/β-catenin, key pathways in regulating tumor proliferation and metastasis, were found to be inactivated by the down-regulation of PBF in ESCA cells. In conclusion, our study demonstrates that PBF functions as a proto-oncogene in ESCA in vitro, which may be mediated through AKT/mTOR and Wnt3a/β-catenin pathways.

Regulation of cell cycle genes during avian neuroretina development

1995 ◽  
Vol 84 (1-2) ◽  
pp. 84-84
Author(s):  
Anne Kastner ◽  
Xavier Espanel ◽  
Germain Gillet ◽  
Gilbert Brun
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Genes ◽  
Regulation Of Cell Cycle
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