scholarly journals Delivery of RIPK4 small interfering RNA for bladder cancer therapy using natural halloysite nanotubes

2019 ◽  
Vol 5 (9) ◽  
pp. eaaw6499 ◽  
Author(s):  
Jianye Liu ◽  
Yi Zhang ◽  
Qinghai Zeng ◽  
Hongliang Zeng ◽  
Xiaoming Liu ◽  
...  

RNA interference (RNAi) technology can specifically silence the expression of a target gene and has emerged as a promising therapeutic method to treat cancer. In the present study, we showed that natural halloysite nanotube (HNT)–assisted delivery of an active small interfering RNA (siRNA) targeting receptor-interacting protein kinase 4 (RIPK4) efficiently silenced its expression to treat bladder cancer. The HNTs/siRNA complex increased the serum stability of the siRNA, increased its circulation lifetime in blood, and promoted the cellular uptake and tumor accumulation of the siRNA. The siRNA markedly down-regulated RIPK4 expression in bladder cancer cells and bladder tumors, thus inhibiting tumorigenesis and progression in three bladder tumor models (a subcutaneous model, an in situ bladder tumor model, and a lung metastasis model), with no adverse effects. Thus, we revealed a simple but effective method to inhibit bladder cancer using RIPK4 silencing, indicating a promising therapeutic method for bladder cancer.

2009 ◽  
Vol 20 (6) ◽  
pp. 589-597 ◽  
Author(s):  
Sridhar Dharmapuri ◽  
Luigi Aurisicchio ◽  
Antonella Biondo ◽  
Natalie Welsh ◽  
Gennaro Ciliberto ◽  
...  

2006 ◽  
Vol 119 (20) ◽  
pp. 1734-1739 ◽  
Author(s):  
Jian-quan HOU ◽  
Jun HE ◽  
Xiao-lin WANG ◽  
Duan-gai WEN ◽  
Zi-xing CHEN

2012 ◽  
Vol 97 (2) ◽  
pp. E282-E291 ◽  
Author(s):  
Lucie Canaff ◽  
Jean-François Vanbellinghen ◽  
Ippei Kanazawa ◽  
Hayeon Kwak ◽  
Natasha Garfield ◽  
...  

Context: In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known. Objective: Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology. Methods: Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells. Results: The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-β up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-β inhibition of cell numbers. Conclusion: When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases.


PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e48567 ◽  
Author(s):  
Sivakamasundari Pichu ◽  
Swapna Krishnamoorthy ◽  
Andrei Shishkov ◽  
Bi Zhang ◽  
Peter McCue ◽  
...  

2021 ◽  
Vol 2 (2) ◽  
pp. 16-19
Author(s):  
Shazia Choudhary ◽  
Sheeba Murad ◽  
Sana Gul ◽  
Hayat Khan ◽  
Samra Khalid ◽  
...  

RNA interference (RNAi) refers to the inhibition of gene expression by small double-stranded RNA molecules. This technology can prove to be a breakthrough biological discovery of the decade as it has the potential to revolutionize the field of therapeutics. RNA interference (RNAi) through small interfering RNA (siRNA) is currently being evaluated for its efficacy to be used in therapeutics as well as prophylactic strategies. Many studies are being conducted across the globe to optimize the siRNA delivery systems (in terms of safe, stable and efficient delivery) in various disorders. There are a number of diseases such as autoimmune diseases, cancer associated pathological changes, bacterial and viral induced disorders, where RNAi pathway can be explored and RNAi technology can be used as a tool to intervene such abnormalities. This review is an effort to review latest advancements in the field of siRNA based therapy development and the pits and falls generally encountered in the use of this technology.


2020 ◽  
Author(s):  
Ubaid Qayoom ◽  
Zahoor Mushtaq

Ribonucleic acid interference (RNAi), a valuable tool for manipulating gene functionality in the laboratory, has also emerged as a powerful tool to suppress infection or replication of many pathogens that cause severe economic losses in fish farming. By taking advantage of the cell’s endogenous RNAi apparatus, small interfering RNA of ~21-22 bp can be introduced into cells to induce target specific mRNA degradation. With the growing appreciation for the potential of RNAi technology, the diversity in vivo relevance to aquaculture is seemingly vast. Studies in the future should address the hurdles like delivery strategy stability and degradation of RNAi therapeutic molecule by nucleases in aquatic animals. In this article, we review the literature in the field of RNAi technology in aquaculture, summarize the status and prospects, which may open doors to its applicability potential as a therapeutic strategy to modulate host-pathogen interactions and inspire further trials.


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