MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer

• DOI: 10.18632/oncotarget.2281
• Publication Date: 2015-09-15T23:38:30Z
• Authors: Sheema Khan; Mara C. Ebeling; Mohd S. Zaman; Mohammed Sikander; Murali M. Yallapu; Neeraj Chauhan; Ashley M. Yacoubian; Stephen W. Behrman; Nadeem Zafar; Deepak Kumar; Paul A. Thompson; Meena Jaggi; Subhash C. Chauhan
• Keywords: Microscopy, Confocal; Reverse Transcriptase Polymerase Chain Reaction; Blotting, Western; Mucins; Fluorescent Antibody Technique; Mice, Nude; Real-Time Polymerase Chain Reaction; Transfection; Immunohistochemistry; 3. Good health; Gene Expression Regulation, Neoplastic; Pancreatic Neoplasms; Mice; MicroRNAs; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Animals; Heterografts; Humans; Neoplasm Invasiveness; In Situ Hybridization; Carcinoma, Pancreatic Ductal

// Sheema Khan 1 , Mara C. Ebeling 2 Mohd S. Zaman Mohammed Sikander Murali M. Yallapu Neeraj Chauhan Ashley Yacoubian 3 Stephen W. Behrman 4 Nadeem Zafar Deepak Kumar 5 Paul A. Thompson 2,6 Meena Jaggi and Subhash Department of Pharmaceutical Sciences Center for Cancer Research, University Tennessee Health Science Center, Memphis, Tennessee, USA Biology Research Sanford Research/USD, Sioux Falls, South Dakota, Pathology, Surgery, Biological Environmental Sciences, the District Columbia, Washington, Columbia 6 Methodology Data Analysis Correspondence: Chauhan, email: Keywords : Pancreatic cancer, MUC13, MicroRNA, Tumor suppressor, Diagnostics, Therapeutics Received June 14, 2014 Accepted July 29, Published 30, Abstract cancer has a poor prognosis due to late diagnosis ineffective therapeutic multimodality. transmembrane mucin is highly involved in pancreatic progression. Thus, understanding its regulatory molecular mechanisms may offer new avenue therapy prevention/treatment cancer. Herein, we report novel microRNA (miR-145)-mediated mechanism regulating aberrant MUC13 expression We that miR-145 inversely correlates with cells human tumor tissues. predominantly present normal tissues early Ductal Adenocarcinoma (PDAC) precursor lesions (PanIN I) progressively suppressed over course development from PanIN II/III stage poorly differentiated PDAC. demonstrate targets 3′ untranslated region thus downregulates protein cells. Interestingly, transfection inhibits cell proliferation, invasion enhances gemcitabine sensitivity. It causes reduction HER2, P-AKT, PAK1 an increase p53. Similar results were found when was specifically inhibited by shRNA directed at MUC13. Additionally, intratumoral injections xenograft mice growth via suppression downstream target, HER2. These suggest as regulator