title: Unveiling the principle of microRNA-mediated redundancy in cellular pathway regulation.
abstract: Understanding the multifaceted nature of microRNA (miRNA) function in mammalian cells is still a challenge. Commonly accepted principles of cooperativity and multiplicity of miRNA function imply that individual mRNAs can be targeted by several miRNAs whereas a single miRNA may concomitantly regulate a subset of different genes. However, there is a paucity of information whether multiple miRNAs regulate critical cellular events and thereby acting redundantly. To gain insight into this notion, we conducted an unbiased high-content miRNA screen by individually introducing 1139 miRNA mimics into Chinese hamster ovary (CHO) cells. We discovered that 66% of all miRNAs significantly impacted on proliferation, protein expression, apoptosis and necrosis. In summary, we provide evidence for a substantial degree of redundancy among miRNAs to maintain cellular homeostasis.
authors.affiliation: a Institute of Applied Biotechnology; University of Applied Sciences Biberach ; Biberach , Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Fischer
authors.forename: René
authors.initials: R
authors.lastname: Handrick
authors.forename: Armaz
authors.initials: A
authors.lastname: Aschrafi
authors.forename: Kerstin
authors.initials: K
authors.lastname: Otte
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016466:CHO Cells; D049109:Cell Proliferation; D051340:Cofilin 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003412:Cricetulus; D015870:Gene Expression; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018716:Molecular Mimicry; D009336:Necrosis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D051340:Cofilin 2; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering
keywords: 3'-untranslated region; 3'UTR; AF647; AlexaFluor→647; CH; CHO; CO2; Chinese hamster; Chinese hamster ovary; Cricetulus griseus; MIR; PI; RNA interference; RNAi; SEAP; base pair; bp; cDNA; carbon dioxide; cgr; chinese hamster ovary; mRNA; mature microRNA; miR; miRNA; microRNA; nc; non-coding; pathway regulation; pre-miR; precursor microRNA; propidium iodide; puro; puromycin; qRT-PCR; quantitative reverse-transcriptase real-time PCR; redundancy; rounds per minute; rpm; screen; secreted alkaline phosphatase; siRNA; small-interfering RNA
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