Inhibitory effect of small interfering RNA specific for a novel candidate target in PB1 gene of influenza A virus

Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA—vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.

Download Full-text

Targeted Small Interfering RNA-Immunoliposomes as a Promising Therapeutic Agent against Highly Pathogenic Avian Influenza A (H5N1) Virus Infection

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02768-13 ◽

2014 ◽

Vol 58 (5) ◽

pp. 2816-2824 ◽

Cited By ~ 16

Author(s):

K. Khantasup ◽

P. Kopermsub ◽

K. Chaichoun ◽

T. Dharakul

Keyword(s):

Virus Infection ◽

Small Interfering Rna ◽

Influenza A ◽

H5n1 Virus ◽

Therapeutic Agent ◽

Highly Pathogenic Avian Influenza ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza ◽

Interfering Rna ◽

Promising Therapeutic Agent

Download Full-text

The FDA-Approved Anti-Asthma Medicine Ciclesonide Inhibits Lung Cancer Stem Cells through Hedgehog Signaling-Mediated SOX2 Regulation

International Journal of Molecular Sciences ◽

10.3390/ijms21031014 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1014 ◽

Cited By ~ 5

Author(s):

Hack Sun Choi ◽

Su-Lim Kim ◽

Ji-Hyang Kim ◽

Dong-Sun Lee

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Small Interfering Rna ◽

Hedgehog Signaling ◽

Underlying Mechanism ◽

Inhibitory Effect ◽

Protein Levels ◽

Lung Cancer Stem Cells ◽

Interfering Rna

Ciclesonide is an FDA-approved glucocorticoid (GC) used to treat asthma and allergic rhinitis. However, its effects on cancer and cancer stem cells (CSCs) are unknown. Our study focuses on investigating the inhibitory effect of ciclesonide on lung cancer and CSCs and its underlying mechanism. In this study, we showed that ciclesonide inhibits the proliferation of lung cancer cells and the growth of CSCs. Similar glucocorticoids, such as dexamethasone and prednisone, do not inhibit CSC formation. We show that ciclesonide is important for CSC formation through the Hedgehog signaling pathway. Ciclesonide reduces the protein levels of GL1, GL2, and Smoothened (SMO), and a small interfering RNA (siRNA) targeting SMO inhibits tumorsphere formation. Additionally, ciclesonide reduces the transcript and protein levels of SOX2, and an siRNA targeting SOX2 inhibits tumorsphere formation. To regulate breast CSC formation, ciclesonide regulates GL1, GL2, SMO, and SOX2. Our results unveil a novel mechanism involving Hedgehog signaling and SOX2 regulated by ciclesonide in lung CSCs, and also open up the possibility of targeting Hedgehog signaling and SOX2 to prevent lung CSC formation.

Download Full-text

Inhibitory effect of small interfering RNA on dengue virus replication in mosquito cells

Virology Journal ◽

10.1186/1743-422x-7-270 ◽

2010 ◽

Vol 7 (1) ◽

pp. 270 ◽

Cited By ~ 24

Author(s):

Xinwei Wu ◽

Hua Hong ◽

Jinya Yue ◽

Yejian Wu ◽

Xiangzhong Li ◽

...

Keyword(s):

Dengue Virus ◽

Virus Replication ◽

Small Interfering Rna ◽

Inhibitory Effect ◽

Mosquito Cells ◽

Interfering Rna

Download Full-text

Flt3 Mutations in Proximity to an Ubiquitin Dependent Endocytosis Motif Suspend Its Hdm2 Modulation.

Blood ◽

10.1182/blood.v110.11.4320.4320 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4320-4320

Author(s):

Line Wergeland ◽

Eystein Oveland ◽

Gry Sjoholt ◽

Siv Lise Bedringaas ◽

Randi T. Hovland ◽

...

Keyword(s):

Small Interfering Rna ◽

Inhibitory Effect ◽

Down Regulation ◽

Reciprocal Regulation ◽

Surface Receptors ◽

Flt3 Mutations ◽

Elevated Expression ◽

Interfering Rna ◽

Small Molecular Inhibitors ◽

Tandem Duplications

Abstract Acute myeloid leukemia (AML) frequently features mutations in the receptor tyrosine kinase Flt3 and elevated expression of the oncogenic E3 ubiquitin ligase Hdm2. Additional to the p53 inhibitory effect of Hdm2, Hdm2 appears involved in endocytosis of cell surface receptors. In this study we explore the possibility of Flt3 modulation by Hdm2 in primary AML cells and cell lines (NB4 and MV4–11) with wild type Flt3 (Flt3-wt) or mutated Flt3 (Flt3-ITD). Flt3 ligand (FL), small molecular inhibitors and small interfering RNA (siRNA) were used to elucidate the relation between Flt3 and Hdm2 on protein level, mRNA expression and modulation of apoptosis. The basal level of Flt3 is higher in AML patients with Flt3-ITD than in patients with Flt3-wt. Flt3-ITD affects a ubiquitin endocytosis motif that in some patients are duplicated, possibly resulting in enhanced receptor cycling. Down-regulation of Flt3-wt by FL, small interfering RNA or PKC412 resulted in elevated level of Hdm2. Similarly, Hdm2 attenuation resulted in increased Flt3 protein expression. Flt3-ITD responded less to Flt3 down-regulation, and was only weakly responding to Hdm2 modulation. We demonstrate that modulation of Flt3 or Hdm2 results in reciprocal regulation, and that Flt3 with internal tandem duplications may suspend its Hdm2 modulation. Together, Flt3-ITD results in dysregulated receptor turnover and elevated Hdm2 thus interconnecting the two pathways of Flt3 and p53, both related to chemoresistance in AML.

Download Full-text