Aldona Jakstaite1, Aurelija Maziukiene2, Giedre Silkuniene2, Kristina Kmieliute2, Albertas Dauksa2,3, Saulius Paskauskas3,4, Antanas Gulbinas2,3, Zilvinas Dambrauskas2,3. 1. Institute for Digestive System Research, Lithuanian University of Health Sciences, Eiveniu str. 4, Kaunas, 50161, Lithuania. aldona.jakstaite@gmail.com. 2. Institute for Digestive System Research, Lithuanian University of Health Sciences, Eiveniu str. 4, Kaunas, 50161, Lithuania. 3. Department of Surgery, Lithuanian University of Health Sciences, Eiveniu str. 2, Kaunas, 50161, Lithuania. 4. Department of Obstetrics and Gynaecology, Lithuanian University of Health Sciences, Eiveniu str. 2, Kaunas, 50161, Lithuania.
Abstract
PURPOSE: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment. METHODS: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein. RESULTS: CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability. CONCLUSION: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.
PURPOSE: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment. METHODS: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein. RESULTS:CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability. CONCLUSION: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.
Authors: Pascal O Berberat; Zilvinas Dambrauskas; Antanas Gulbinas; Thomas Giese; Nathalia Giese; Beat Künzli; Frank Autschbach; Stefen Meuer; Markus W Büchler; Helmut Friess Journal: Clin Cancer Res Date: 2005-05-15 Impact factor: 12.531
Authors: Malisetty V Swamy; Bhargava Citineni; Jagan M R Patlolla; Altaf Mohammed; Yuting Zhang; Chinthalapally V Rao Journal: Nutr Cancer Date: 2008 Impact factor: 2.900
Authors: Jacob New; Dharmalingam Subramaniam; Satish Ramalingam; Jonathan Enders; Afreen Asif Ali Sayed; Sivapriya Ponnurangam; David Standing; Prabhu Ramamoorthy; Maura O'Neil; Dan A Dixon; Subhrajit Saha; Shahid Umar; Sumedha Gunewardena; Roy A Jensen; Sufi Mary Thomas; Shrikant Anant Journal: Mol Carcinog Date: 2019-04-24 Impact factor: 4.784