title: The polymorphic terminal-loop of pre-miR-1307 binding with MBNL1 contributes to colorectal carcinogenesis via interference with Dicer1 recruitment.
abstract: Colorectal cancer (CRC) is one of the most common malignancies in the world. Studies have demonstrated that single nucleotide polymorphisms (SNPs) in microRNA genes (miRSNPs) are involved in the occurrence of cancers. However, the relationship between the miRSNPs within the terminal-loops of microRNA precursors and the development of CRC is still largely unknown. In this study, we found that a miRSNP rs7911488 T>C in the terminal-loop of pre-miR-1307 was significantly associated with the occurrence of CRC. The C allele of rs7911488 is more prevalent in CRC patients than in healthy controls (P < 0.001), and this C allele prevalence is related to low level of miR-1307 expression. A RNA-binding protein MBNL1 binds with a 'UGCUGC' motif in the terminal-loop of the C-allelic pre-miR-1307 and blocks Dicer processing, resulting in downregulation of miR-1307 expression. Consequently, the antiapoptosis protein Bcl2, which is a direct target of miR-1307, is overexpressed in CRC. Furthermore, MBNL1 participates in processing of both C-allelic and T-allelic pre-miR-1307. In summary, our results show that rs7911488 C-allelic pre-miR-1307 binds to MBNL1 and infers with Dicer processing, leading to reduced miR-1307 and increased Bcl2 expression, thus representing an important process in the initiation of CRC.
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China, Department of Oncology and Department of Clinical Laboratory, the Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China, Department of Gastroenterology and Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210000, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of Oncology and.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Oncology and.
authors.forename: Ruirong
authors.initials: R
authors.lastname: Wu
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China, Department of Oncology and Department of Clinical Laboratory, the Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China, Department of Gastroenterology and Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210000, China.
authors.forename: Xinru
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Oncology and.
authors.forename: Dongjuan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, the Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Oncology and.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Gastroenterology and.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology and.
authors.forename: Weichang
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Oncology and.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China, Department of Oncology and Department of Clinical Laboratory, the Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China, Department of Gastroenterology and Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210000, China.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China, Department of Oncology and Department of Clinical Laboratory, the Fourth Affiliated Hospital of Soochow University, Wuxi 214062, China, Department of Gastroenterology and Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of Soochow University, Suzhou 215006, China and Department of Pharmacy, Jiangsu Cancer Hospital, Nanjing 210000, China wangweipeng@suda.edu.cn.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Wang
mesh_terms: D020121:5' Untranslated Regions; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; C000595707:BCL2 protein, human; C493663:MBNL1 protein, human; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D016601:RNA-Binding Proteins; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases