scholarly journals MicroRNA-520a suppresses HBV replication in HepG2.2.15 cells by inactivating AKT

2018 ◽  
Vol 46 (11) ◽  
pp. 4693-4704 ◽  
Author(s):  
Wei Sun ◽  
Jinqian Zhang ◽  
Jinglong Chen
Keyword(s):  
Serine Threonine Kinase ◽  
Laboratory Methods ◽  
Threonine Kinase ◽  
Hbv Replication ◽  
B Virus ◽  
Hepatocellular Carcinoma Cell Line ◽  
Polymerase Chain ◽  
Novel Target ◽  
Interfering Rna ◽  
Transcription And Replication

Objective To investigate whether the mechanism by which a microRNA, miR-520a, suppresses the replication of hepatitis B virus (HBV) involves the regulation of the serine/threonine kinase ( AKT) gene. Methods The effects of miR-520a on the proliferation, mitotic index and apoptosis of the HBV-replicating human hepatocellular carcinoma cell line HepG2.2.15 were measured using standard laboratory methods including flow cytometry. The effects of miR-520a on HBV transcription and replication were assessed using methods including immunoassays and reverse transcription–polymerase chain reaction. The effect of small interfering RNA (siRNA) to AKT on the levels of AKT mRNA and protein were also evaluated. Results In HepG2.2.15 cells, miRNA-520a reduced HBV transcription and replication by reducing AKT levels. MiRNA-520a decreased cell proliferation and mitosis entry of cells and increased apoptosis in HepG2.2.15 cells. AKT levels were reduced significantly by its siRNA, which resulted in suppression of HBV replication in HepG2.2.15 cells. Conclusions MiRNA-520a inhibited AKT gene expression and suppressed HBV transcription and replication. These findings suggest that miRNA-520a may be a novel target for the treatment of HBV infection because miRNA-520a reduced HepG2.2.15 cell survival and inhibited HBV replication associated with the AKT signalling pathway.

scholarly journals In Situ Hybridization Analysis of ZPK Gene Expression During Murine Embryogenesis

1997 ◽  
Vol 45 (1) ◽  
pp. 107-118 ◽  
Author(s):  
André Nadeau ◽  
Gilles Grondin ◽  
Richard Blouin
Keyword(s):  
In Situ Hybridization ◽  
Northern Blot Analysis ◽  
Spatial And Temporal Patterns ◽  
Serine Threonine Kinase ◽  
Teratocarcinoma Cell ◽  
Threonine Kinase ◽  
Cell Lineages ◽  
Polymerase Chain

ZPK is a recently described protein serine/threonine kinase that has been originally identified from a human teratocarcinoma cell line by the polymerase chain reaction and whose function in signal transduction has not yet been elucidated. To investigate the potential role of this protein kinase in developmental processes, we have analyzed the spatial and temporal patterns of expression of the ZPK gene in mouse embryos of different gestational ages. Northern blot analysis revealed a single mRNA species of about 3.5 KB from Day 11 of gestation onwards. In situ hybridization studies demonstrated strong expression of ZPK mRNA in brain and in a variety of embryonic organs that rely on epithelio-mesenchymal interactions for their development, including skin, intestine, pancreas, and kidney. In these tissues, the ZPK mRNA was localized primarily in areas composed of specific types of differentiating cells, and this expression appeared to be upregulated at a time concomitant with the onset of terminal differentiation. Taken together, these observations raise the possibility that the ZPK gene product is involved in the establishment and/or maintenance of a fully cytodifferentiated state in a variety of cell lineages.

scholarly journals Neurogenesis and Increase in Differentiated Neural Cell Survival via Phosphorylation of Akt1 after Fluoxetine Treatment of Stem Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anahita Rahmani ◽  
Danial Kheradmand ◽  
Peyman Keyhanvar ◽  
Alireza Shoae-Hassani ◽  
Amir Darbandi-Azar
Keyword(s):  
Survival Rate ◽  
Cell Survival ◽  
Neural Cell ◽  
Neural Cells ◽  
Chain Reaction ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Fluoxetine Treatment ◽  
Polymerase Chain

Fluoxetine (FLX) is a selective serotonin reuptake inhibitor (SSRI). Its action is possibly through an increase in neural cell survival. The mechanism of improved survival rate of neurons by FLX may relate to the overexpression of some kinases such as Akt protein. Akt1 (a serine/threonine kinase) plays a key role in the modulation of cell proliferation and survival. Our study evaluated the effects of FLX on mesenchymal stem cell (MSC) fate and Akt1 phosphorylation levels in MSCs. Evaluation tests included reverse transcriptase polymerase chain reaction, western blot, and immunocytochemistry assays. Nestin, MAP-2, andβ-tubulin were detected after neurogenesis as neural markers. TenμM of FLX upregulated phosphorylation of Akt1 protein in induced hEnSC significantly. Also FLX did increase viability of these MSCs. Continuous FLX treatment after neurogenesis elevated the survival rate of differentiated neural cells probably by enhanced induction of Akt1 phosphorylation. This study addresses a novel role of FLX in neurogenesis and differentiated neural cell survival that may contribute to explaining the therapeutic action of fluoxetine in regenerative pharmacology.

The hepatitis B virus-encoded transcriptional trans-activator hbx appears to be a novel protein serine/threonine kinase

Cell ◽  
1990 ◽  
Vol 63 (4) ◽  
pp. 687-695 ◽  
Author(s):  
Jane Y. Wu ◽  
Zhuo-Yuan Zhou ◽  
Amrit Judd ◽  
Christine A. Cartwright ◽  
William S. Robinson
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
B Virus ◽  
Novel Protein

scholarly journals A Role for Taok2 in Listeria monocytogenes Vacuolar Escape

2020 ◽  
Author(s):  
Juan J Quereda ◽  
Camille Morel ◽  
Noelia Lopez-Montero ◽  
Jason Ziveri ◽  
Steven Rolland ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Kinase Activity ◽  
Bacterial Pathogen ◽  
Host Factors ◽  
Host Cells ◽  
Listeriolysin O ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Activity Inhibition ◽  
Interfering Rna

Abstract The bacterial pathogen Listeria monocytogenes invades host cells, ruptures the internalization vacuole, and reaches the cytosol for replication. A high-content small interfering RNA (siRNA) microscopy screen allowed us to identify epithelial cell factors involved in L. monocytogenes vacuolar rupture, including the serine/threonine kinase Taok2. Kinase activity inhibition using a specific drug validated a role for Taok2 in favoring L. monocytogenes cytoplasmic access. Furthermore, we showed that Taok2 recruitment to L. monocytogenes vacuoles requires the presence of pore-forming toxin listeriolysin O. Overall, our study identified the first set of host factors modulating L. monocytogenes vacuolar rupture and cytoplasmic access in epithelial cells.

scholarly journals The Transcriptional Transactivation Function of HBx Protein Is Important for Its Augmentation Role in Hepatitis B Virus Replication

2005 ◽  
Vol 79 (9) ◽  
pp. 5548-5556 ◽  
Author(s):  
Hong Tang ◽  
Luvsanjav Delgermaa ◽  
Feijun Huang ◽  
Naoki Oishi ◽  
Li Liu ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Cell Line ◽  
Luciferase Reporter ◽  
Transactivation Domain ◽  
Alanine Scanning Mutagenesis ◽  
Hbv Replication ◽  
Transcriptional Transactivation ◽  
B Virus ◽  
Transcription And Replication

ABSTRACT The role and functional domain of hepatitis B virus (HBV) X protein (HBx) in regulating HBV transcription and replication were investigated with a transient transfection system in the human hepatoma cell line HepG2 using wild-type or HBx-minus HBV genome constructs and a series of deletion or mutation HBx expression plasmids. We show here that HBx has augmentation effects on HBV transcription and replication as a HBV mutant genome with defective X gene led to decreased levels of 3.5-kb HBV RNA and HBV replication intermediates and that these decreases can be restored by either transient ectopic expression of HBx or a stable HBx expression cell line. The C-terminal two-thirds (amino acids [aa] 51 to 154), which contain the transactivation domain, is required for this function of HBx; the N-terminal one-third (aa 1 to 50) is not required. Using the alanine scanning mutagenesis strategy, we demonstrated that the regions between aa 52 to 65 and 88 to 154 are important for the augmentation function of HBx in HBV replication. By the luciferase reporter gene analysis, we found that the transactivation and coactivation activities of HBx coincide well with its augmentation function in HBV transcription and replication. These results suggest that HBx has an important role in stimulating HBV transcription and replication and that the transcriptional transactivation function of HBx may be critical for its augmentation effect on HBV replication.

scholarly journals VISTA, PDL-L1, and BRAF—A Review of New and Old Markers in the Prognosis of Melanoma

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 74
Author(s):  
Andreea Cătălina Tinca ◽  
Iuliu Gabriel Cocuz ◽  
Mihaela Cornelia Șincu ◽  
Raluca Niculescu ◽  
Adrian Horațiu Sabău ◽  
...  
Keyword(s):  
T Cell Activation ◽  
Cell Activation ◽  
Prognostic Markers ◽  
Malignant Tumors ◽  
Medical Field ◽  
Invasive Potential ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Programmed Death ◽  
Novel Target

Melanoma is currently known as one of the most aggressive malignant tumors. The prognostic factors and particularities of this neoplasm are a persistent hot topic in the medical field. This review has multiple purposes. First, we aim to summarize the known data regarding the histological and immunohistochemical appearance of this versatile tumor and to look further into the analysis of several widely used prognostic markers, such as B-Raf proto-oncogene, serine/threonine kinase BRAF. The second purpose is to analyze the data on the new prognostic markers, V-domain Immunoglobulin Suppressor of T cell Activation (VISTA) and Programmed death-ligand 1 (PD-L1). VISTA is a novel target that is considered to be highly important in determining the invasive potential and treatment response of a melanoma, and there are currently only a limited number of studies describing its role. PD-L1 is a marker with whose importance has been revealed in multiple types of malignancies, but its exact role regarding melanoma remains under investigation. In conclusion, the gathered data highlights the importance of correlations between these markers toward providing patients with a better outcome.

scholarly journals ETV7 is an essential component of a rapamycin-insensitive mTOR complex in cancer

2018 ◽  
Vol 4 (9) ◽  
pp. eaar3938 ◽  
Author(s):  
Franklin C. Harwood ◽  
Ramon I. Klein Geltink ◽  
Brendan P. O’Hara ◽  
Monica Cardone ◽  
Laura Janke ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Paradigm Shift ◽  
Transcriptional Activity ◽  
Human Cancer ◽  
Serine Threonine Kinase ◽  
Threonine Kinase ◽  
Mechanistic Target Of Rapamycin ◽  
Tumor Onset ◽  
Novel Target ◽  
Rapamycin Resistance

The mechanistic target of rapamycin (mTOR) serine/threonine kinase, a critical regulator of cell proliferation, is frequently deregulated in human cancer. Although rapamycin inhibits the two canonical mTOR complexes, mTORC1 and mTORC2, it often shows minimal benefit as an anticancer drug. This is caused by rapamycin resistance of many different tumors, and we show that a third mTOR complex, mTORC3, contributes to this resistance. The ETS (E26 transformation–specific) transcription factor ETV7 interacts with mTOR in the cytoplasm and assembles mTORC3, which is independent of ETV7’s transcriptional activity. This complex exhibits bimodal mTORC1/2 activity but is devoid of crucial mTORC1/2 components. Many human cancers activate mTORC3 at considerable frequency, and tumor cell lines that lose mTORC3 expression become rapamycin-sensitive. We show mTORC3’s tumorigenicity in a rhabdomyosarcoma mouse model in which transgenic ETV7 expression accelerates tumor onset and promotes tumor penetrance. Discovery of mTORC3 represents an mTOR paradigm shift and identifies a novel target for anticancer drug development.

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