An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation

1988 ◽  
Vol 8 (2) ◽  
pp. 963-973
Author(s):  
J T Holt ◽  
R L Redner ◽  
A W Nienhuis
Keyword(s):  
Cell Growth ◽  
Protein Concentration ◽  
Myeloid Differentiation ◽  
Sequence Specificity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Steady State Levels ◽  
Cell Growth And Differentiation ◽  
Antisense Oligomer

To study the role of a nuclear proto-oncogene in the regulation of cell growth and differentiation, we inhibited HL-60 c-myc expression with a complementary antisense oligomer. This oligomer was stable in culture and entered cells, forming an intracellular duplex. Incubation of cells with the anti-myc oligomer decreased the steady-state levels of c-myc protein by 50 to 80%, whereas a control oligomer did not significantly affect the c-myc protein concentration. Direct inhibition of c-myc expression with the anti-myc oligomer was associated with a decreased cell growth rate and an induction of myeloid differentiation. Related antisense oligomers with 2- to 12-base-pair mismatches with c-myc mRNA did not influence HL-60 cells. Thus, the effects of the antisense oligomer exhibited sequence specificity, and furthermore, these effects could be reversed by hybridization competition with another complementary oligomer. Antisense inhibition of a nuclear proto-oncogene apparently bypasses cell surface events in affecting cell proliferation and differentiation.

scholarly journals An oligomer complementary to c-myc mRNA inhibits proliferation of HL-60 promyelocytic cells and induces differentiation.

1988 ◽  
Vol 8 (2) ◽  
pp. 963-973 ◽  
Author(s):  
J T Holt ◽  
R L Redner ◽  
A W Nienhuis
Keyword(s):  
Cell Growth ◽  
Protein Concentration ◽  
Myeloid Differentiation ◽  
Sequence Specificity ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Steady State Levels ◽  
Cell Growth And Differentiation ◽  
Antisense Oligomer

To study the role of a nuclear proto-oncogene in the regulation of cell growth and differentiation, we inhibited HL-60 c-myc expression with a complementary antisense oligomer. This oligomer was stable in culture and entered cells, forming an intracellular duplex. Incubation of cells with the anti-myc oligomer decreased the steady-state levels of c-myc protein by 50 to 80%, whereas a control oligomer did not significantly affect the c-myc protein concentration. Direct inhibition of c-myc expression with the anti-myc oligomer was associated with a decreased cell growth rate and an induction of myeloid differentiation. Related antisense oligomers with 2- to 12-base-pair mismatches with c-myc mRNA did not influence HL-60 cells. Thus, the effects of the antisense oligomer exhibited sequence specificity, and furthermore, these effects could be reversed by hybridization competition with another complementary oligomer. Antisense inhibition of a nuclear proto-oncogene apparently bypasses cell surface events in affecting cell proliferation and differentiation.

scholarly journals Distribution of basic fibroblast growth factor in the 18-day rat fetus: localization in the basement membranes of diverse tissues.

1990 ◽  
Vol 110 (3) ◽  
pp. 753-765 ◽  
Author(s):  
A M Gonzalez ◽  
M Buscaglia ◽  
M Ong ◽  
A Baird
Keyword(s):  
Cell Types ◽  
Wide Distribution ◽  
Basement Membranes ◽  
Specific Staining ◽  
Rat Fetus ◽  
Basic Fgf ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Cell Growth And Differentiation

Immunohistochemical methods were used to study the distribution of basic FGF in the 18-d rat fetus. The results reveal a pattern of widespread yet specific staining that is consistent with the wide distribution of basic FGF. Immunoreactive basic FGF is associated with mesenchymal structures, mesoderm- and neuroectoderm-derived cells, and their extracellular matrices. As an example, skeletal and smooth muscle cells are strongly positive. The basement membrane underlying the epithelia always contain basic FGF. In some tissues (i.e., cartilage and bone) the intensity of immunostaining is dependent on the stage of cell differentiation. Although the staining of tissues is primarily associated with the extracellular matrix, there is significant intracellular staining in various cell types. This is particularly evident in the endocrine cells of the adrenal cortex, testis, and ovary. The histochemical findings reported here support the notion that basic FGF has the characteristics required to mediate many of the effects of the mesenchyme on cell growth and differentiation. The significance of these findings in understanding the role of basic FGF in regulating cell proliferation and differentiation is discussed.

scholarly journals Integrity of the short arm of nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation

2020 ◽  
Author(s):  
Alba Gonzalez-Estevez ◽  
Annalisa Verrico ◽  
Clarisse Orniacki ◽  
Bernardo Reina-San-Martin ◽  
Valérie Doye
Keyword(s):  
Cell Growth ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Proliferation And Differentiation ◽  
Mild Reduction ◽  
Cell Growth And Differentiation ◽  
Pore Complexes

SUMMARYNuclear pore complexes (NPCs) are established players in cell division and differentiation. However studies on the contribution of individual NPC subunits to these processes are still scarce. Here we use mouse embryonic stem cells (mESCs) to characterize the role of NPC structural components, focusing on the short arm of the Y-complex that comprises Nup85, Seh1 and Nup43. We show that Seh1 and Nup43, although dispensable at the pluripotent stage, are required for normal cell growth rates, and for mESC viability upon differentiation. mESCs lacking Seh1 or Nup43 display a mild reduction of NPC density that is also observed in an N-terminally truncated Nup85 mutant in which interaction with Seh1 is greatly impaired. However, mESC proliferation and differentiation are not altered in these Nup85 mutant cells, indicating that it is the integrity of the Y-complex, rather than the number of NPCs, that is critical to ensure these processes.

Role of microRNAs in myeloid differentiation

2008 ◽  
Vol 36 (6) ◽  
pp. 1201-1205 ◽  
Author(s):  
Alessandro Fatica ◽  
Alessandro Rosa ◽  
Monica Ballarino ◽  
Maria Laura De Marchis ◽  
Kasper D. Rasmussen ◽  
...  
Keyword(s):  
Cell Fate ◽  
Ectopic Expression ◽  
The Body ◽  
Molecular Networks ◽  
Myeloid Differentiation ◽  
Molecular Tools ◽  
Proliferation And Differentiation ◽  
Cell Growth And Differentiation ◽  
Therapeutic Tools

All types of blood cell of the body are continuously produced by rare pluripotent self-renewing HSCs (haemopoietic stem cells) by a process known as haemopoiesis. This process provides a valuable model for examining how genetic programmes involved in cell differentiation are established, and also how cell-fate specification is altered in leukaemia. Here, we describe examples of how miRNAs (microRNAs) can influence myelopoiesis and how the identification of their target mRNAs has contributed to the understanding of the molecular networks involved in the alternative control between cell growth and differentiation. Ectopic expression and knockdown of specific miRNAs have provided powerful molecular tools able to control the switch between proliferation and differentiation, therefore providing new therapeutic tools for interfering with tumorigenesis.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

scholarly journals The Role of the Hedgehog Pathway in Cholangiocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4774
Author(s):  
Giulia Anichini ◽  
Laura Carrassa ◽  
Barbara Stecca ◽  
Fabio Marra ◽  
Chiara Raggi
Keyword(s):  
Anticancer Agents ◽  
Cell Biology ◽  
Detailed Knowledge ◽  
Molecular Features ◽  
Cell Proliferation And Differentiation ◽  
Predominant Type ◽  
Proliferation And Differentiation ◽  
Cholangiocarcinoma Cell ◽  
Hh Signaling

Cholangiocarcinoma (CCA) is a poorly treatable type of cancer and, along with hepatocellular carcinoma (HCC), is the predominant type of primitive liver cancer in adults. The lack of understanding of CCA biology has slowed down the identification of novel targets and the development of effective treatments. While tumors share some general characteristics, detailed knowledge of specific features is essential for the development of effectively tailored therapeutic approaches. The Hedgehog (HH) signaling cascade regulates stemness biology, embryonal development, tissue homeostasis, and cell proliferation and differentiation. Its aberrant activation has been associated with a variety of solid and hematological human malignancies. Several HH-inhibiting compounds have been indeed developed as potential anticancer agents in different types of tumors, with Smoothened and GLI inhibitors showing the most promising results. Beside its well-established function in other tumors, findings regarding the HH signaling in CCA are still controversial. Here we will give an overview of the most important clinical and molecular features of cholangiocarcinoma, and we will discuss the available evidence of the crosstalk between the HH signaling pathway and the cholangiocarcinoma cell biology.

Role of miR-214 in biomaterial transplantation therapy for osteonecrosis

2021 ◽  
pp. 1-13
Author(s):  
Yuying Wang ◽  
Rui He ◽  
Anqi Yang ◽  
Rui Guo ◽  
Jie Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Scaffold ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells ◽  
Transplantation Therapy ◽  
Cells Cultured ◽  
In Cells

BACKGROUND: The effectiveness and availability of conservative therapies for osteonecrosis of the femoral head (ONFH) are limited. Transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with Bio-Oss, which is a good bone scaffold biomaterial for cell proliferation and differentiation, is a new potential therapy. Of note, the expression of miRNAs was significantly modified in cells cultured with Bio-Oss, and MiR-214 was correlated positively with osteonecrosis. Furthermore, miR-214 was upregulated in cells exposed to Bio-Oss. OBJECTIVE: To investigate whether targeting miR-214 further improves the transplantation effect. METHODS: We treated BMSCs with agomiR-214 (a miR-214 agonist), antagomiR-214 (a miR-214 inhibitor), or vehicle, followed by their transplantation into ONFH model rats. RESULTS: Histological and histomorphometric data showed that bone formation was significantly increased in the experimental groups (Bio-Oss and BMSCs treated with antagomiR-214) compared with other groups. CONCLUSIONS: miR-214 participates in the inhibition of osteoblastic bone formation, and the inhibition of miR-214 to bone formation during transplantation therapy with Bio-Oss combined with BMSCs for ONFH.

scholarly journals MicroRNAs in brain development and cerebrovascular pathophysiology

2019 ◽  
Vol 317 (1) ◽  
pp. C3-C19 ◽  
Author(s):  
Qingyi Ma ◽  
Lubo Zhang ◽  
William J. Pearce
Keyword(s):  
Brain Development ◽  
Synapse Formation ◽  
Current Knowledge ◽  
Great Promise ◽  
Ischemic Brain ◽  
Neural Lineage ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
And Function

MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs with 21–25 nucleotides in length and play an important role in regulating gene expression at the posttranscriptional level via base-paring with complementary sequences of the 3′-untranslated region of the target gene mRNA, leading to either transcript degradation or translation inhibition. Brain-enriched miRNAs act as versatile regulators of brain development and function, including neural lineage and subtype determination, neurogenesis, synapse formation and plasticity, neural stem cell proliferation and differentiation, and responses to insults. Herein, we summarize the current knowledge regarding the role of miRNAs in brain development and cerebrovascular pathophysiology. We review recent progress of the miRNA-based mechanisms in neuronal and cerebrovascular development as well as their role in hypoxic-ischemic brain injury. These findings hold great promise, not just for deeper understanding of basic brain biology but also for building new therapeutic strategies for prevention and treatment of pathologies such as cerebral ischemia.

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