Sinan Sun1, Tianyi Hang2, Boyu Zhang3, Liang Zhu4, Yang Wu4, Xiangwei Lv4, Qiang Huang4, Hanhui Yao4. 1. Medical College of Shandong University Jinan, Shandong Province, P. R. China. 2. Department of Health Management Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui Province, P. R. China. 3. The Second Hospital of Anhui Medical University Hefei, Anhui Province, P. R. China. 4. Department of General Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui Province, P. R. China.
Abstract
BACKGROUND: Colon cancer, or colorectal cancer (CRC), is a type of cancer that develops from large bowel. Previous data has demonstrated that microRNAs (miRNAs) may be involved in the formation and progression of CRC. The deregulation of miR-708 has been identified in multiple types of cancer. However, to the best of our knowledge, there are no data concerning the expression and role of miR-708 in CRC. METHODS: In this study, RT-PCR and Flow Cytometry were used to examine the expression and role of miR-708 and ZEB1 in proliferation and apoptosis. Transwell was used to examine the role of miR-708 and ZEB1 in invasion and migration. Western blot and qRT-PCR were conducted to determine the alteration of protein and miR-708 levels, respectively. RESULTS: MiR-708 was significantly downregulated in CRC tissues and cell lines. The restoration of the expression of miR-708 suppressed cell proliferation, induced apoptosis, and reduced metastasis in CRC in vitro. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-708. Furthermore, ZEB1 was upregulated in CRC, which was negatively correlated with miR-708 expression. Further studies showed that the overexpression of miR-708 and silence of ZEB1 inhibited stage of CRC via inhibiting AKT/mTOR signaling pathway in CRC cells. CONCLUSION: Taken together, these results indicate that miR-708 plays an important role in suppressing the development of CRC by directly targeting ZEB1 through AKT/mTOR signaling pathway, suggesting that miR-708 is a novel, effective therapeutic target for treating patients with CRC. AJTR
BACKGROUND:Colon cancer, or colorectal cancer (CRC), is a type of cancer that develops from large bowel. Previous data has demonstrated that microRNAs (miRNAs) may be involved in the formation and progression of CRC. The deregulation of miR-708 has been identified in multiple types of cancer. However, to the best of our knowledge, there are no data concerning the expression and role of miR-708 in CRC. METHODS: In this study, RT-PCR and Flow Cytometry were used to examine the expression and role of miR-708 and ZEB1 in proliferation and apoptosis. Transwell was used to examine the role of miR-708 and ZEB1 in invasion and migration. Western blot and qRT-PCR were conducted to determine the alteration of protein and miR-708 levels, respectively. RESULTS:MiR-708 was significantly downregulated in CRC tissues and cell lines. The restoration of the expression of miR-708 suppressed cell proliferation, induced apoptosis, and reduced metastasis in CRC in vitro. Additionally, bioinformatics analysis predicted ZEB1 as a novel target gene of miR-708. Furthermore, ZEB1 was upregulated in CRC, which was negatively correlated with miR-708 expression. Further studies showed that the overexpression of miR-708 and silence of ZEB1 inhibited stage of CRC via inhibiting AKT/mTOR signaling pathway in CRC cells. CONCLUSION: Taken together, these results indicate that miR-708 plays an important role in suppressing the development of CRC by directly targeting ZEB1 through AKT/mTOR signaling pathway, suggesting that miR-708 is a novel, effective therapeutic target for treating patients with CRC. AJTR
Authors: Patrick A Kenney; Matthew F Wszolek; Kimberly M Rieger-Christ; Brasil Silva Neto; Justin J Gould; Niall J Harty; Juan Miguel Mosquera; Ron Zeheb; Massimo Loda; Douglas S Darling; John A Libertino; Ian C Summerhayes Journal: BJU Int Date: 2010-08-24 Impact factor: 5.588
Authors: Amelia Cimmino; George Adrian Calin; Muller Fabbri; Marilena V Iorio; Manuela Ferracin; Masayoshi Shimizu; Sylwia E Wojcik; Rami I Aqeilan; Simona Zupo; Mariella Dono; Laura Rassenti; Hansjuerg Alder; Stefano Volinia; Chang-Gong Liu; Thomas J Kipps; Massimo Negrini; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2005-09-15 Impact factor: 11.205