title: Post-transcriptional regulation of the tumor suppressor miR-139-5p and a network of miR-139-5p-mediated mRNA interactions in colorectal cancer.
abstract: MicroRNAs play key roles in many biological processes, and are frequently dysregulated in tumor cells. However, there are few studies on how microRNAs are dysregulated. miR-139-5p, an important tumor suppressor, is often underexpressed in gastrointestinal cancer cells. Here, we describe post-transcriptional regulation of this intronic microRNA in human colorectal cancer. miR-139-5p is expressed independently of its overexpressed host gene PDE2A in colorectal cancer tissues and cell lines. The miR-139-5p target genes IGF1R, ROCK2 and RAP1B exert regulatory effects on the miR-139-5p expression level, relying on their ability to compete for miR-139-5p binding. These overexpressed target genes also regulate each others' protein levels through 3'-UTRs, thus regulating tumor cell growth and motility properties. Our study provides a mechanistic, experimentally validated rationale for intronic microRNA dysregulation in colorectal cancer, revealing novel oncogenic roles of IGF1R, ROCK2 and RAP1B 3'-UTRs.
authors.affiliation: Department of Molecular & Cellular Pharmacology, Biomedical Nanotechnology Center, State Key Laboratory of Bioreactor Engineering & Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, PR, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Shen
authors.forename: Rurong
authors.initials: R
authors.lastname: Mao
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Yueqi
authors.initials: Y
authors.lastname: Li
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Qiu
authors.forename: Daling
authors.initials: D
authors.lastname: Cui
authors.forename: Vanminh
authors.initials: V
authors.lastname: Le
authors.forename: Peihao
authors.initials: P
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Ni
authors.forename: Jianwen
authors.initials: J
authors.lastname: Liu
mesh_terms: D020413:3' Untranslated Regions; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics*; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2 / Q000235:genetics / Q000378:metabolism; D004843:Epistasis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D020413:3' Untranslated Regions; C555098:MIRN139 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D054678:Cyclic Nucleotide Phosphodiesterases, Type 2; C517275:PDE2A protein, human
keywords: 3′-UTR; colorectal cancer (CRC); competing endogenous RNA (ceRNA); miR-139-5p; post-transcriptional regulation