Type

Journal Article

Authors

Jochen H M Prehn
Caoimhin G Concannon
Zebunnissa Ramtoola
Annette T Byrne
Frank Murray
Deborah A McNamara
Elaine W Kay
Ritesh Pabari
Niamh McCawley
Lorna Flanagan
and 1 others

Subjects

Biochemistry

Topics
cancer targeting cell proliferation cancer cells colorectal cancer crc gene silencing cancer treatment colon cancer endoplasmic reticulum stress

Targeting the 19S proteasomal subunit, Rpt4, for the treatment of colon cancer. (2015)

Abstract Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Caoimhin G Concannon, Zebunnissa Ramtoola, Annette T Byrne, Frank Murray, Deborah A McNamara, Elaine W Kay, Ritesh Pabari, Niamh McCawley, Lorna Flanagan and 1 others

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
CaoimhĂ­n G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
3
Zebunnissa Ramtoola
Royal College of Surgeons in Ireland
Total Publications: 21
 
4
Annette T Byrne
Royal College of Surgeons in Ireland
Total Publications: 41
 
5
F E Murray
Royal College of Surgeons in Ireland
 
6
Deborah A McNamara
Royal College of Surgeons in Ireland
Total Publications: 17
 
7
Elaine W Kay
Royal College of Surgeons in Ireland
Total Publications: 157
 
8
Ritesh M Pabari
Royal College of Surgeons in Ireland
Total Publications: 21
 
9
Niamh McCawley
Royal College of Surgeons in Ireland
Total Publications: 9
 
10
Lorna Flanagan
Royal College of Surgeons in Ireland
Total Publications: 23