
Mechanisms of Oncogenesis by miR-155 The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Witten, Lisa Walker. 2019. Mechanisms of Oncogenesis by miR-155. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:42029676 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA ! ! ! ! "#$%&'()*)!+,!+'$+-#'#)()!./!*(01233! ! "!#$%%&'()($*+!,'&%&+(&#! -.! /$%)!0)12&'!0$((&+! (*! 34&!5$6$%$*+!*7!8&#$9)1!:9$&+9&%! $+!,)'($)1!7;17$11<&+(!*7!(4&!'&=;$'&<&+(%!! 7*'!(4&!#&>'&&!*7!! 5*9(*'!*7!?4$1*%*,4.! $+!(4&!%;-@&9(!*7!! A$*1*>$9)1!)+#!A$*<&#$9)1!:9$&+9&%! ! ! ! ! B)'6)'#!C+$6&'%$(.! D)<-'$#>&E!8)%%)94;%&((%! 8)'94!FGHI ! ! ! ! ! ! ! ! ! J!FGHI!/$%)!0)12&'!0$((&+! "11!'$>4(%!'&%&'6&#K! ! ! 5$%%&'()($*+!"#6$%*'L!M')+2!:1)92!! ! ! ! ! /$%)!0)12&'!0$((&+! ! 8&94)+$%<%!*7!*+9*>&+&%$%!-.!<$NOHPP! ! !"#$%&'$( 3;<*'%!#&6&1*,!Q4&+!)-+*'<)1$($&%!$+!)!9&11!)99;<;1)(&!(*!,'*<*(&!>'*Q(4!)+#! ,'&6&+(! #&)(4K! 34&%&! )-+*'<)1$($&%! 9)+! $+91;#&! <;()($*+%! *'! 94)+>&%! $+! >&+&! &R,'&%%$*+K!S+&!(.,&!*7!7)9(*'!(4)(!9)+!9*+('$-;(&!(*!(;<*'!#&6&1*,<&+(!$%!<$9'*NT"%! U<$NT"%VE!Q4$94!)'&!%<)11!+*+O9*#$+>!NT"%!(4)(!'&,'&%%!&R,'&%%$*+!*7!()'>&(!>&+&%K! <$NOHPP!$%!)+!$+71)<<)($*+O)%%*9$)(&#!<$NT"!(4)(!)9(%!)%!)+!*+9*>&+&!$+!)!+;<-&'!*7! 4&<)(*1*>$9)1! <)1$>+)+9$&%K! B&'&E! Q&! &R)<$+&! (4&! <*1&9;1)'! <&94)+$%<%! -.! Q4$94! <$NOHPP!9)+!,'*<*(&!(;<*'!#&6&1*,<&+(!)+#!,'*>'&%%$*+K!! 0&!;%&#!)+!$+#;9$-1&!(')+%>&+$9!<*;%&!<*#&1!(4)(!*6&'&R,'&%%&%!<$NOHPP!)+#! #&6&1*,%! 4&<)(*1*>$9)1! <)1$>+)+9.! (*! ;+#&'%()+#! 4*Q! 9**,&')($*+! -&(Q&&+! <;1($,1&! <$NOHPP! ()'>&(%! #'$6&%! *+9*>&+&%$%K! S+&! 9)(&>*'.! *7! <$NOHPP! ()'>&(%! $+91;#&%! 5T"! '&,)$'!7)9(*'%E!%*!Q&!,&'7*'<&#!Q4*1&!&R*<&!%&=;&+9$+>!*+!(;<*'%!7'*<!*;'!<*;%&! <*#&1!)+#!$#&+($7$&#!)!%$+>1&!*+9*>&+&E!$14(5E!Q4$94!7'&=;&+(1.!UWIXYV!-*'&!)9($6)($+>! <;()($*+%K! 3;<*'! >'*Q(4! Q)%! #&,&+#&+(! *+! (4$%! $14(5! )9($6$(.E! )%! ('&)(<&+(! Q$(4! )+! $+4$-$(*'!'&%;1(&#!$+!'),$#!(;<*'!'&>'&%%$*+K!B*Q&6&'E!(4&!<;()($*+!$%!+*(!%;77$9$&+(!7*'! (;<*'!>'*Q(4!Q4&+!<$NOHPP!$%!+*(!*6&'&R,'&%%&#E!-&9);%&!#&)9($6)($+>!(4&!<$NOHPP! (')+%>&+&! )1%*! '&%;1(%! $+! (;<*'! '&>'&%%$*+K! 0&! %4*Q&#! (4)(! $14(5! &R,'&%%$*+! $%! #&,&+#&+(! *+!<$NOHPP! &R,'&%%$*+E! $+#$9)($+>! (4)(! ()'>&(%!*7! <$NOHPP! (4)(! )77&9(! $14(5! ! $$$! &R,'&%%$*+!<;%(!9**,&')(&!<$NOHPPO#'$6&+!5T"!'&,)$'!#&7$9$&+9.!$+!*'#&'!7*'!(;<*'%!(*! 7*'<!)+#!,'*>'&%%K!! ?'&1$<$+)'.! #)()! 7'*<! 7;'(4&'! %(;#$&%! %;>>&%(! (4)(! (4$%! <&94)+$%<! *7! *+9*>&+&%$%! $%! )6)$1)-1&! *+1.! ;+#&'! 9&'()$+! 9*+#$($*+%K! M*'! $+%()+9&E! $14(5! <).! -&! &,$>&+&($9)11.!%$1&+9&#!$+!)#;1(!<$9&E!,'&6&+($+>!'&>;1)($*+!*7!$(%!&R,'&%%$*+!-.!<$NOHPPK! 34$%!<&94)+$%<!$%!)1%*!+*(!)6)$1)-1&!Q4&+!%&1&9($*+!,'&%%;'&!$%!),,1$&#!-.!&R(&+#&#! ('&)(<&+(!Q$(4!%<)11!<*1&9;1&!$+4$-$(*'%E!)+#!;+#&'!(4&%&!9*+#$($*+%E!*(4&'!<&94)+$%<%! %&&<!(*!-&!)6)$1)-1&!7*'!<$NOHPP!(*!,'*<*(&!*+9*>&+&%$%K!M;(;'&!'&%&)'94!9*;1#!7*9;%! *+! $#&+($7.$+>! )+#! ;+#&'%()+#$+>! (4&%&! )##$($*+)1! <&94)+$%<%! )+#! (4&! 9*+(&R(%! $+! Q4$94!(4&.!)'&!;($1$Z&#K!! 0&!,'&%&+(!4&'&!)!+&Q!<*#&1!7*'!<;1($O%(&,!*+9*>&+&%$%!-.!)!<$NT"E!$+!Q4$94! <;1($,1&!()'>&(%!9**,&')(&!(*!#'$6&!*+9*>&+&%$%K!34$%!<*#&1!<).!-&!),,1$9)-1&!(*!*(4&'! <$NT"%!)+#!9*;1#!$+7*'<!(4&!;%&!*7!<$NT"%!)%!-$*<)'2&'%!)+#!(4&'),&;($9%K!! ! ( ! $6! )&"*+(,-(.,/$+/$#( ! !"#$%&'$(000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(111! )&"*+(,-(.,/$+/$#(0000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(2! !'3/,4*+56+7+/$#(00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(21! .8&9$+%(:;(</$%,5='$1,/(000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(:! S6&'6$&Q!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!F! 3;<*'!#&6&1*,<&+(!)+#!>'*Q(4!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!F! 8$9'*NT"!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK![! <$NT"!$+!D)+9&'!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!HG! <$NOHPP!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!HX! B&<)(*,*$&%$%!)+#!B&<)(*1*>$9)1!8)1$>+)+9$&%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!HI! 9O\$(!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!FH! S-@&9($6&%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!FX! .8&9$+%(>;(71?@:AA(5%12+#(,/',6+/+#1#("B(9%,7,$1/6(&/5(',,9+%&$1/6(41$8( 7=$&$1,/#(1/($8+("#$%&(,/',6+/+00000000000000000000000000000000000000000000000000000000000000000000000000000000(>C! "-%(')9(!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!FP! ]+('*#;9($*+!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!F^! N&%;1(%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!F_! 5$%9;%%$*+!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!`I! .8&9$+%(D;(E/9="*1#8+5(?+#=*$#(00000000000000000000000000000000000000000000000000000000000000000000000000000000(A>! ]+('*#;9($*+!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!PX! N&%;1(%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!PX! 5$%9;%%$*+!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK![X! .8&9$+%(C;(F+$8,5#00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(GH! .8&9$+%(A;(I1#'=##1,/(000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(JK! D**,&')($*+!-&(Q&&+!<$NT"!()'>&(%!$+!*+9*>&+&%$%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!IG! <$NOHPP!)+#!9O\$(!$+!9)+9&'!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!IF! 3')+%7&9($*+!*7!4&<)(*1*>$9)1!9&11%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!IP! <$NT"%!)+#!#';>!'&%$%()+9&!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!I^! D*+91;%$*+%!KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK!II! ?+-+%+/'+#(00000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000000(:LL! ! ( ! 6! !'3/,4*+56+7+/$#( ! ( ]!4)6&!-&&+!$+9'&#$-1.!1;92.!(*!-&!%;''*;+#&#!-.!%;94!)+!$+9'&#$-1&!9*<<;+$(.! *7!%9$&+($%(%!#;'$+>!<.!?45K!34)+2!.*;!7*'!-&$+>!<.!<&+(*'%E!7'$&+#%E!)+#!$+%,$')($*+K!! 3*!<.!)#6$%*'E!5'K!M')+2!:1)92E!]!)<!%*!>')(&7;1!(*!4)6&!-&&+!,)'(!*7!.*;'!1)-K!a*;'! <&+(*'%4$,E!%;,,*'(E!)+#!>;$#)+9&!Q&'&!91&)'E!9*+%$%(&+(E!&+9*;')>$+>E!)+#!,')9($9)1K! a*;!7*%(&'&#!)+!&+6$'*+<&+(!Q4&'&!]!7&1(!Q&19*<&#E!9*+7$#&+(E!%;,,*'(&#E!$+#&,&+#&+(E! )+#!$+(&11&9(;)11.!&+>)>&#K!3*!!(4&!<&<-&'%!*7!(4&!:1)92!1)-E!]!)<!(4)+27;1!(*!4)6&!4)#! .*;! (*! Q*'2E! ()12E! @*2&E! 9*<<$%&')(&E! 9*11)-*')(&E! )+#! 1&)'+! Q$(4! &6&'.! #).! Q4$1&! ,&'7*'<$+>!(4$%!'&%&)'94E!)+#!]b<!,'*;#!(*!9)11!<.%&17!)!:1)92&'K!3*!(4&!<&<-&'%!*7!<.! )#6$%*'.! 9*<<$((&&E! 5'K! 8)((4&Q! 8&.&'%*+E! 5'K! \)'&+! D$94*Q%2$E! )+#! 5'K! c;#.! /$&-&'<)+E!(4)+2!.*;!7*'!.*;'!$+(&'&%(!$+!<.!,'*@&9(!)+#!$+!<.!%;99&%%E!)+#!7*'!(4&!($<&! )+#!>;$#)+9&!.*;!,'*6$#&#!(*Q)'#!<.!)99*<,1$%4<&+(%K!3*!<.!7)<$1.E!]!)<!%*!-1&%%&#! (*!4)6&!-&&+!')$%&#!$+!%;94!)+!$+=;$%$($6&!)+#!9;'$*;%!4*;%&4*1#E!)+#!(*!4)6&!4)#!.*;'! $+7&9($*;%!&+(4;%$)%<!7*'!1&)'+$+>!&+9*;')>$+>!<&!(4'*;>4!(4$%!'&%&)'94K!M$+)11.E!c)9*-E! .*;!4)6&!-&&+!&6&'.(4$+>!]!+&&#&#!)(!&6&'.!%()>&!*7!<.!?45E!)+#!]b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
Details
-
File Typepdf
-
Upload Time-
-
Content LanguagesEnglish
-
Upload UserAnonymous/Not logged-in
-
File Pages116 Page
-
File Size-