ForummiRNA–MicrobiotaInteractioninGutHomeostasisandColorectalCancerJiayiDong,1JesseW.Tai,1andLi-FanLu1,2,3,*Guthomeostasisismaintainedbydy-namichost–microbiotainteractions.Recently,miRNAshaveemergedaskeymolecularregulatorsinthemedia-tionofsuchinteractions.Here,wediscusstheroleofahostmiRNA–microbiomeaxisinguthomeostasisandcolorectalcancer(CRC)andtheinvolvementofdietandmicrobialme-tabolitesinmiRNA-mediatedintestinalhealth.IntroductionInteractionsbetweenthehostandgutmicrobiotaarecrucialforshapingguthomeostasisandimmuneresponse.Dysbiosisofgutmicrobiotahasbeenlinkedtovariousgastrointestinal(GI)diseases,includingcolorectalcancer(CRC).Itisclearthathost–gutmicro-biotacommunicationrequiresacomplicatedandelaborateregulatorynetwork.Recently,miRNAshaveemergedasimportantmediatorsofthiscommunication.miRNAsareatypeofshortnoncodingRNA(�21–25nucleotides)thatplayimportantrolesingeneregulationatboththepost-transcriptionalandtranslationallevel.Inthepastseveralyears,manygroupshaveextensivelyexaminedthefunc-tionsofmiRNAinimmunecellsandin-testinalepithelialcellsintheGItract(re-viewedin[1]).Moreover,theimportanceofmiRNAsinhost–microbiotainteractionsandtheirimpactonintestinalhomeostasisandgut-associatedcancershavealsobeguntobeappreciated(Figure1).MicrobialImpactonHostmiRNAinCRCAplethoraofstudiessuggestalinkbe-tweenintestinaldysbiosisandCRC.Somehavereporteddistinctmicro-biome‘fingerprints’associatedwithdifferentsubtypesofCRC[2].Othersshowedthespecificenrichmentofplau-siblyoncogenicmicrobesinCRCcasescomparedwithcontrols.Tothisend,onemicrobethathasbeenheavilylinkedwithCRCisFusobacteriumnu-cleatum.RecentliteraturehasalsoimplicatedF.nucleatum’seffectsonthehostmiRNomeasonepotentialma-jorcontributor.Inonestudy,F.nucleatumwasshowntoincreaseCRCcellproliferationandtumorgrowthinmicebyupregulatingmiR-21intumorcellsbyactivatingtheTLR4–MyD88signalingcascade[3].Mechanistically,oninductionmiR-21targetedandreducedtheproteinlevelsofRASA1andPDCD4,bothofwhicharetumorsuppressorgenes.Consis-tently,...
