Ozel Capik1,2, Fatma Sanli1,2, Ali Kurt3, Onur Ceylan4, Ilknur Suer5, Murat Kaya5, Michael Ittmann6,7, Omer Faruk Karatas8,9. 1. Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey. 2. Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey. 3. Department of Pathology, Erzurum Faculty of Medicine, Health Sciences University, Erzurum, Turkey. 4. Department of Pathology, Faculty of Medicine, Ataturk University, Erzurum, Turkey. 5. Department of Internal Medicine, Division of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 6. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA. 7. Michael E. DeBakey VAMC, Houston, TX, USA. 8. Molecular Biology and Genetics Department, Erzurum Technical University, Erzurum, Turkey. faruk.karatas@erzurum.edu.tr. 9. Molecular Cancer Biology Laboratory, High Technology Application and Research Center, Erzurum Technical University, Erzurum, Turkey. faruk.karatas@erzurum.edu.tr.
Abstract
BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancer in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells. METHODS: We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models. RESULTS: In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway. CONCLUSION: In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.
BACKGROUND: Prostate cancer (PCa) is the most common malignancy diagnosed among men after lung cancer in developed countries. Investigation of the underlying molecular mechanisms of PCa is urgently needed in order to develop better therapeutic strategies and to reveal more effective therapeutic targets. In this study, we aimed at exploring the potential functions of CASC11 in association with miR-145 and IGF1R during the malignant progression of PCa cells. METHODS: We initially investigated the oncogenic potential of noncoding members of CASC gene family and analyzed the effects of CASC11 overexpression on proliferation, migration, and colony formation ability of DU145, LNCaP, and PC3 PCa cells. We, then, exprlored the association of CASC11, miR-145, and IGF1R expression and their impacts on PI3K/AKT/mTOR signaling pathway in in vitro models. RESULTS: In silico analysis revealed that of the CASC family only CASC11 showed consistent results considering its differential expression as well as its association with the overall survival of patients. We demonstrated that ectopic overexpression of CASC11 significantly increased the proliferation, colony formation, and migration capacity in all three cell lines. CASC11 overexpression caused suppression of miR-145 and overexpression of IGF1R, leading to activation of PI3K/AKT/mTOR signaling pathway. CONCLUSION: In summary, we found that CASC11 is upregulated in PCa cells and clinical tumor samples in comparison to corresponding controls and revealed that ectopic CASC11 overexpression promotes cellular phenotypes associated with PCa progression through CASC11/miR-145/IGF1R axis.