国外大学申请Proposal.docx

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1、Coding-independentregulationofcoloncancercellproliferationPROJECTDESCRIPTIONColorectalCancer(CRC),amalignantdiseasederivedfromcolonepithelialcells,isoneofthemajorthreatstopublichealth.AustraliahasoneofthehighestratesofCRCintheworld.Itisthethirdmostcommontypeofnewlydiagnosedcancerinthec

2、ountry.Moreover,itisthesecondmostcommoncancerkiller,claiminglivesofaround3982Australianseachyear.However,thereiscurrentlynocurativetreatmentformetastaticcolorectalcancers.InvestigationofgenesandsignalingpathwaysthataredysregulatedinCRCisahighpriorityforidentificationofnoveltherapeutict

3、argets.Only1.5%ofthemammaliangenomeencodesproteins,andmostofthegenomeistranscribedtotensofthousandsoflong(>200nt)non-codingRNAs(lncRNAs).However,thefunctionalconsequenceoftheexpressionoflncRNAshasbeenlargelyuncharacterized.Todate,averysmallnumberoflncRNAshavebeeninvestigated,andtheirfu

4、nctionalroles,revealed,incoloncancer.PreliminarystudiesfromProfessorXuDongZhang’slaboratoryhaveshownthattheexpressionofalncRNAcalledREG1CPiselevatedinfiveCRCtissuesincomparisonwithadjacentnon-cancerouscolonepithelialtissues.TheincreaseinREG1CPisfurtherconfirmedinapanelofCRCcelllinescom

5、paredwithanormalhumancoloncelllineFHC.Ofnote,inhibitionofREG1CPbysiRNAreduced,whereasoverexpressionofREG1CPenhanced,CRCcellproliferation.ToturnthisinformationintoouradvantageinunderstandingCRCbiologyandinthetreatmentofthedisease,weproposeinthisapplicationtoclarifytheconsequenceofREG1CP

6、upregulationandthemechanisminvolvedinCRCcells,andtoexaminewhetherREG1CP-mediatedsignalisapotentialtherapeutictargetinCRC.OurspecificaimsaretotestwhethertargetingREG1CPinhibitsproliferationofCRCcellsandretardsCRCxenograftgrowthinanimalmodels,andtodefinethemechanismthatdrivestheincreasei

7、nREG1CPexpressioninCRCcellsandthemechanismbywhichREG1CPregulatescoloncancergrowth.UniversityofNewcastlehasastrongcancerresearchprogramaimingtotranslatescientificadvancesintobetterclinicalcare.ThisprojectfitsperfectlytotheobjectivesofCancerPrograminthatitwillpotentiallyleadtothedevelo