JH u a z hongU n ivS c iT e c hno l[M e dS c i ] 34 ( 2 ) :2 07 21 2 , 2 01 4 DO I10 . 10 07 / s1 15 9 6 -0 14 -1 26 0 x JH u a z hongU n ivS c iT e c hno l [M e dS c i] 34 (2 ) :2 01 4

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* M i c r oRNA 215I saP o t en t ia lP r ognos t i c Ma rk e rfo rC e rv i ca lCan c e r 1 2# 1 1 Hu aL IANG(梁 华) ,Y anL I( 李 艳) ,Ruo yuLUO( 洛若愚) ,F u j i nSHEN( 申复进) 1 2 D epa r tm en to fOb s t e t r i c sandG yn e co log y ,D epa r tm en to fC l in i ca lLabo ra to r y ,R enm inHo sp i ta lo fW uhanUn i v e r s i t y ,W uhan 430060 ,Ch ina

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Summa ry :R e c en t l y ,m i c roRNA s(m iRNA s )h av eb e enshowntob einvo lv edin m u l t ip l eb io log i c a l p a thw ay sth a tc anin f lu en c etumo rp rog r e s s ionandm e t a s t a s i sandth eyc ans e rv ea sp rogno s t i cb io m a rk e r sin m an yc an c e r s .Th ep r e s en ts tud yex am in ed th ep rogn o s t i cs ign i f i c an c eo fm iR -215inc e rv i c a lc an c e r .Th ep a r a f f in em b edd edp a i r edc e rv i c a ls c r ap es am p l e sandtum o rt i s s u es am p l e sf rom302 p a t i en t sw i ths t ag eI Ic e rv i c a lc an c e rw e r ed e t e c t edfo rth eexp r e s s iono fm iR -215b yu s ingqRT -PCR .A m iR -215 -b a s edc l a s s i f i e rw a se s t ab l i sh edb yu s ingth eCoxr eg r es s ion mod e l .Th ep rogno s t i can dp r e d i c t iv ea c cu r a c yo fth i sc l a s s i f i e rw a sd e t e rm in edinbo thth ein t e r n a lt e s t ingg roupo f138p a t i en t s ,and th eex t e rn a lind ep end en tg roupo f280p a t i en t s . Mo r eov e r ,c e rv i c a lc an c e rH eL ac e l l sov e r exp r e s s ing m iR -215(H eL a -m iR -215 )w e r econ s t ru ct edandsub cu t an eou s lyin j e c t edin toth enud em i c etoex am in e th ee f f e c to fm iR -215ontumo rg row thand m e t a s t a s i sinv i vo .Th er e s u l t ss how edth a tth eex p r e s s ion l ev e lo fm iR -21 5w a ss ign i f i c an t lyh igh e rinc e rv i c a lc an c e rt i s s u e sth aninp a i r edno rm a lt i s s u e s ( P50 58 80 T umo rs i z e( cm ) 0 .21 4 51 75 >4 84 92 F IGOs t ag e 0 .002 Lowr i s k 1 1 1 1 1 1 H ighr i sk 24 56 H i s to log i c a lg r ad e(F IGO ) 0 .037 Lowr i sk 90 54 H ighr i sk 45 1 13 V a s cu l a rinv a s io n 0 .02 No tp r e s en t 69 63 104 P r e s en tb 66 L ymphno d em e t a s t a s i s 0 .04 N eg a t iv e 58 53 Po s i t iv e 77 1 14 ER 0 .35 Lowexp r e s s ion 72 98 H ighexp r e s s ion 63 69 PR 0 .90 Lowexp r e s s ion 71 89 H ighexp r e s s ion 64 78 ER :e s t rog enr e c ep to r ;PR :p rog e s t e ron er e c ep to r .aM ed i anw a su s eda scu to f fv a l u e . bV a s cu l a rinv a s iono ftumo rc e l l sw e r ed e t e c t ed in 2v e s s e l s .

2 .2R i skS c o r e so fm iR 215inC e r v i ca lCan c e r B yu s i n gX t i l ep l o t st og e n e r a t et h eop t im umc u t o f f s c o r e ,t h ep a t i e n t sw i t har i s ks c o r eo f0o rh i g h e rw e r e a l l o c a t edt ot h eg r ou po fp a t i e n t sa th i g hr i s ko fd i s e a s e r e cu r r e n c e( h igh r i s kg ro u p ) ,an dt h o s ew i thar i s ks co r e l ow e rt h a n0t ot h eg ro u pa tl owr i s ko fd i s e a s er e c u r r en c e( low r i s kg roup ) .Th ep rogno s t i ca c cu r a cyo fth e m iR -215 -b a s e d c l a s s i f i e r w a s a s s e s s ed by

t im e d e p e n d e n tROCa n a l y s i sa tv a r y i n gf o l l ow u pt im e ( f i g . 1A ) .T h ed i s t r i b u t i ono fc l i n i c o p a t h o l o g i c a lc h a r a c t e r i s t i c sd i dn o tv a rys i gn i f i c an t l yb e tw e e nt h eh i gh r i s k a ndl ow r i s kg r o up( t a b l e1 ) .T h e5 -y e a rd i s e a s e f r e e s u r v i v a lw a s4 3%( 9 5% C I3 2 . 1– 5 1 . 6 )fo rt h eh i g h r i s k g r o up ,a nd67%( 9 5% C I :48 . 6 – 77 . 3 )f o rt h el ow r i s k g roupa ndth e r ew a sas i gn i f i c an td i f f e r e n c e(h a z a rdr a t io [HR ]2 . 0 2 ,95%C I :1 . 16 – 3 . 5 2 ;P= 0 . 01 3 )( f i g .1B ) .

F ig .1 R i sks co r e sb yth em iR -2 15b a s edc l a s s i f i e r A :T im e -d ep end en tROCcu rv e s .A r e aund e rth ecu rv e(AUC s )a t 3and5y e a r sw e r eu s edtoa s s e s sp rogno s t i ca c cu r a cy .B : K ap l an -M e i e rs u rv iv a linth et r a in ing ,in t e rna lt e s t ing ,andind ep end en tv a l id a t ions e t s .P v a lu e sw e r ec a l cu l a t edu s ingth e log r ankt e s t .

2 . 3Su rv i va lAna l y s e s T h e7 2 -m o n t ho v e r a l ls u r v i v a lr a t eo fc e r v i c a lc a n c e r p a t i e n t sw i t hh i g hm iR 2 1 5e x p r e s s i o n( 7 6 . 1 5% )w a ss i g n i f i c a n t l yh i g h e rt h a nt h a to fp a t i e n t sw i t hl ow m iR 2 1 5 e x p r e s s i o n( 5 8 . 1 2% ;P< 0 . 0 0 0 1 ) .F o rp a t i e n t sw i t hTNM

s t a g eT 3c a n c e r ,t h es u r v i v a lr a t ef o rh i g h -a n dl ow r i s k g r o u p sw a s4 3%( 9 5%C I :3 0 . 7 – 5 0 . 2 )a n d8 9%( 9 5%C I : 6 7 . 3 – 9 2 . 1 3 )(HR3 . 3 1 ,9 5% C I :1 . 1 8 – 5 . 1 4 ;P= 0 . 0 1 7 )r e s p e c t i v e l y( f i g .2A ) .T h es u r v i v a lr a t e sf o rp a t i e n t sw i t h TNMs t a g eT 4c a n c e rw e r e3 8%( 9 5%C I :2 1 . 8 – 4 9 . 4 )a n d

21 0 7 9%( 5 9 . 2 – 8 8 . 9 )f o rt h eh i g h -a n dl ow r i s kg r o u p s(HR : 3 . 4 8 ,9 5%C I :1 . 4 9 – 4 . 4 5 ;P= 0 . 0 0 0 8 )( f i g .2B ) .W h e np a t i e n t sw e r eg r o u p e dt ol owa n dh i g ht um o rg r a d eb yF IGO g r a d i n gs y s t em ,t h es u r v i v a lr a t e sw e r e4 8%( 9 5% C I : 2 9 . 3 – 6 2 . 6 )a n d7 6%( 9 5% C I :5 6 . 5 – 8 9 . 6 )f o rh i g h -a n d

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l ow r i s kg r o u p s(HR2 . 4 0 ,9 5%C I :1 . 2 5 – 3 . 5 3 ;P= 0 . 0 0 5 8 ) i np a t i e n t sw i t hl ow g r a d et um o r s( f i g .2C ) ,a n d5 7% ( 9 5% C I4 2 . 2 – 6 5 . 1 )a n d7 6%( 9 5% C I :5 3 . 3 – 9 0 . 4 )f o r h i g h -a n dl ow r i s kg r o u p s(HR1 . 8 5 ,9 5%C I :1 . 0 2 – 3 . 0 3 ; P= 0 . 0 4 6 1 )i np a t i e n t sw i t hh i g h g r a d et um o r s( f i g .2D ) .

F ig .2 K ap l an -M e i e rs u rv iv a lr a t e K ap l an -M e i e rsu rv iv a lan a ly s i sw a sp e r fo rm edina l lc e rv i c a lc an c e rp a t i en t su sing m iR -215 -b a s edc l a s s i f i e rs t r a t i f i edb yc l in i cop a tho log i c a lr i s kf a c to r s .A :TNMs t ag eT3 ;B :TNMs t ag eT4 ;C :Lowg r ad etum o r ;D :H ighg r ad etum o r .Th eP v a lu e s w e r ec a l cu l a t edu s ingth elog r an kt e s t .

2 . 4E f f e c to fm iR 21 5onC e l lG r ow thand M e t a s t a s i s Th etum o r s ob t a in e df rom m i c ein j e c t ed w i th H eL a -m iR 21 5c e l l sw e r es i g n i f i c a n t l yl a r g e rt h a nt h o s e 2 v s . f rom m i c ein j e c t ed w i thc on t r o lc e l l s( 3 . 5 7± 0 . 47cm 2 ,P= 0 . 0 0 32 )( f i g .3 ) . M o r e ov e r ,i tw a s 1 . 52± 0 . 14cm foundth a tH eL a -m iR -215c e l l sfo rm eda m e a su r ab l e

tum o re a r l i e rt h anth econ t ro lc e l l s ,sugg e s t i ngah igh e r g r ow t hr a t eo fH eL a -m iR -215c e l l scom p a r ed w i t hc on t r o lc e l l s( f i g .3 )o v e rt im e .Fu r t h e rm o r e ,t h eov e r a l ls u r v i v a lr a t ef o rm i c ei n j e c t e dw i t hH eL a -m iR 2 15 w a sd e c r e a s ed(26 .3% )com p a r ed w i t hm i c ei n j e c t e dw i t hc on t ro lc e l l s(76 . 9% )( P= 0. 00 7 ) .

F ig .3 Th eg row thand m e t a s t a s i so fc e rv i c a lc an c e rc e l l sinnud em i c e A :th esub cu t an eou stumo r sob t a in edf romm i c ein j e c t edw i thH eL a -m iR -215c e l l s(down )andco n t ro l(up ) .B :th eexp r e s s ion l ev e lo fm iR -215intumo r sob t a in edf rom m i c ein j e c t edw i thH eL a -m iR -215c e l l sandcon t ro l ,C :th eg row tho fc e rv i c a lH eL a c e l l sinnud em i c e .

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3D ISCUSS ION G row i nge v id en c eh a sd em on s t r a t edth a tm iRNA s a r ee xp r e s s e da b e r r a n t l yi nhum anc a n c e r s ,s u gg e s t ing th a tm iRNA sm ayp l ayap i vo t a lro l ei nc an c e rp a t ho [18 ] .T h em iRNAe xp r e s g en e s i s ,i nv a s i ona nd m i g r a t i on s i onp r o f i l i ng m a yb eu s edt od i s t i ng u i s ht um o rsub t y p e s , d e t e rm i n ep ro gn o s i sa n dp r e d i c tr e s p o n s et os p e c i f i c [19 ] c a n c e rt h e r a p i e s .D u et ot h ea d v a n t a g e so fe a s yd e t e c t i onan dl e s sd e g r a d a t i o n ,m iRNA sh av eb e enr e po r t edt o b em a rk e r sfo rt um o rd e v e l o pm en t ,p ro g r e s s i on ,p r o gn o [2 0 ] .S of a r ,t h e r ei sap a u c i t yo fd a t ao nt h e s i s ,andsoon r o l eo fm iR 2 15i nt h ep r e d i c t i ono ft h ep r o gn o s i so f p a t i en t sw i thc e rv i c a lc a n c e r . m iR -215h a sb e ensh ownt or e gu l a t et h ee x p r e s s i o n o fg e n e sl i n k e dt ot h ed e v e l opm e n t ,p ro g r e s s i o na n d e c en ts tud i e sshow ed p r o gn o s i so fp r o s t a t ec an c e r[21–23].R th a tm iR -215 w a s down r e gu l a t edi ns e v e r a lc an c e r s , [24 ] [25 ] ,co l ont um o r . su c ha so e s o ph ag e a lad e no c a r c inom a How e v e r , som es t ud i e ss how e dt h a t m iR -215 w a s up r e gu l a t edi ns e v e r a lc a n c e r s ,s u c ha sg a s t r i cc a n [26 ] [27 ] ,andp ro s t a t ec an c e r .Ino u rp r e v i ou ss t u d y ,w e c e r s d e t e c t e dm iR -21 5e x p r e s s i o ni n30c e rv i c a lc an c e rt i s su e sa n dt h e i rad j a c e n tno n t um o rt i s su e san df o un dt h a t m iR -215 w a sup r e gu l a t edi nt um o rt i s su e s wh e nc om p a r e dw i t hn on t um o rt i s su e s(d a t an o tshow n ) .T h e ov e r e xp r e s s i o no fm iR -215w a sr e l a t e dt ot h ep r og e s s i o n o fc an e r ,i n d i c a t i ngi t sim po r t a n tr o l ea sano n c og e n ei n [26 ] .T h eu p r e g u l a t e dm iR -2 15c o u l d c an c e rp rog r e s s ion p r o v i d en o v e ld i ag no s t i candp r o gn o s t i ct oo l st oa s s i s ti n t h er e c og n i t i o no fp r o s t a t ec a n c e r sw i t ha gg r e s s i v eb e [27 ] . Inth ep r e s en ts t udy , w efo u ndt h a tt h e h av i o r m iR -215e xp r e s s ion w a ss i gn i fi c a n t l yg r e a t e ri nc e r v i c a l t um o r sw i t hv a s c u l a ri n v a s i o na n da tF IGOs t a g e ,a n dt h e 5 -y e a rd i s e a s e f r e es u rv i v a lw a slow e rinth ep a t i en t s w i t ho v e r e xp r e s s i ono fm iR -2 1 5 .T h et um o rs i z ew a s g r e a t e ri nn u d em i c ei n j e c t e dw i t hH eL a -m iR 215c e l l s t h a ni nt h o s ei n j e c t e dw i t hc on t r o lc e l l s8 w e e k sa f t e r i n j e c t i o n .A l lt h e s ef i nd i ng si nd i c a t edt h a tm iR -215 m a y b e com eapo t e n t i a lun f avo r ab l em a rk e rfo rt h ep r og n o s i s o fc e r v i c a lc a n c e r . T h es t a t i s t i c a lm od e lo ft h eL e a s tA b s o l u t eS h r i n k ag ea n dS e l e c t ionOp e r a to r(L ASSO )m od e li so f t e nu s e d toc l a s s i fyt h ed i s e a s ew i thth ea ido fb iom a rk e r st op r e [28 ] u s edt h e d i c tt h ep ro g no s i so rr i s kf a c t o r s .M a r i s ae ta l LASSO m od e lt oc l a s s i f yt heco lonc an c e rin to m o l e cu l a rsu b t y p e st h r o ug ht h eg e n ee xp r e s s i on so f BRAF , KRAS ,a nd TP5 3 ,w h i c hc o u l db eu s e dt op r e d i c tt h e p r o gn o s i so fc o l o n .B yu s i n gt h eLASSO m od e l ,K e l l e y [29 ] p r e d i c t e dt h ec l i n i c a landp a t ho l og i cr i skf a c t o r s e ta l [30 ] u s e d fo rs t ag eI Ic o lonc a n c e r .R e c en t ly ,Zh ange ta l t h e LASSO m od e lt o bu i l dac l a s s i f i e rb a s e do ns i x m iRNA s ,i n c l ud i ng m iR -21 5 ,an dco n c l u d edt h a tt h i s c l a s s i f i e ri sar e l i a b l ep ro g n o s t i ca n dp r e d i c t i v et oo lf o r d i s e a s er e cu r r e n c einp a t i e n t sw i ths t ag eⅡco lonc a n c e r . Inou rs tudy ,w ea l soe s t ab l i s h eda m iR -215 -b a s e dc l a s s i f i e rt oi d e n t i f yt h ec e r v i c a lc a n c e rp a t i e n t sa th i gh e rr i s k o fr e c u r r e n c e ,andfoundth a tth em iR -215i sa s so c i a t e d w i t hp r o g r e s s i onan dw o r s es u r v i v a lo fc e r v i c a lc a n c e r . Ins umm a ry ,i nt h ep r e s en ts t udy ,w ed em on s t r a t ed th a tm iR -215 w a sov e r e x p r e s s edinc e rv i c a lc an c e rt i s su e s .I tw a ss i gn i f i c a n t lya s s o c i a t e dw i t hF IGOs t a g e , h i s t o l o g i c a lg r ad e ,v a s c u l a ri nv a s i onan dl ym ph n od e

2 1 1 m e t a s t a s i so fc e rv i c a lc a n c e r.B a s eo na m iR 2 1 5c l a s s i f i e r ,i tw a sfoundt h a tth e5 -y e a rsu rv iv a lr a t ew a slow e r inth es t ag eI Ic e rv i c a lc an c e rp a t i e n t sw i t ho v e r e x p r e s s iono fm iR -215 .Ou rfo l low i ngs t ud i e sw i l lfo c u sonu s e o fm iR -21 5 b a s edc l a s s i f i e rt op r ed i c tt h er e sp o n s eo f p a t i en t sw i thc e rv i c a lc an c e rtoa d juv an tch em o th e r apy i no r d e rt oo p t im i z ep e r s o n a l i z e dd r u gt r e a tm e n t sf o r c e r v i c a lc a n c e rp a t i e n t s .A n dl a r g es am p l es i z e sw i l lb e em p loy edt oe x am in eth ep r e c i s em e ch an i smby wh i c h m iR 215i si n v o l v e di nt h ec e r v i c a lc a n c e r . Con f l i c to fIn t e r e s tS ta t em en t Th eau tho r sd e c l a r eth a tth e r ei snocon f l i c to fin t e r e s t w i than yf in an c i a lo r g an i z a t iono r co rpo r a t iono rind iv idu a lth a t c anin app rop r i a t e lyin f lu en c eth i swo rk . REFERENCES 1 S c h i f fm a n M , S o l om o n D .C l in i c a l p r a c t i c e . C e rv i c a l c an c e rs c r e en ing w i t h hum an p ap i l l om av i ru s andcy to log i cco t e s t ing . N Eng lJ M ed ,2013 ,369 (24 ) : 2324 -2331 2 Zh ang Q ,L iu D ,H ang C ,e ta l .P r im a r ys c r e en ingfo r b r e a s td i s e a s e samong17618 w om enin W u f enga r e a ,a r eg ion w i thh ighin c id en c eo fc e rv i c a lc an c e rinCh in a .J Hu a zhong Un iv S c iT e chno l[M ed S c i ] , 201 2 ,32 (2 ) : 252 -256 3 P a r e j aR ,R endo nG J ,S an z -Lom an aCM ,e ta l .S u r g i c a l , on co log i c a l ,an d ob s t e t r i c a l ou t com e sa f t e rab dom in a l r ad i c a lt r a ch e l e c tom y as y s t em a t i cl i t e r a tu r er ev i ew . G yn e co lOn co l ,2013 ,131 (1 ) :77 82 4 Chm u r aA ,W o j c i e s z ek A ,M ro c h emJ ,e ta l .U s e fu ln e s s o fth eSCC ,CEA ,CYFRA21 .1 ,andCRPm a rk e r sfo rth e d i agno s i s and mon i to r ing o fc e rv i c a l squ amou sc e l l c a r c inom a .G in e ko lPo l ,2009 ,80 (5 ) :361 -366 5 V o lgg e rB ,A sp i s i r eng i lC ,G en s e r -K r imb a ch e rE ,e ta l . P rogno s t i cs ign i f i c an c eo fTP Av e r su sSCC -Ag ,CEAand n eop t e r ininc a r c inom ao fth eu t e r in ec e rv ix .C an c e rL e t t , 2008 ,262 (2 ) :183 -189 6 Z h a n gY ,W an gX ,M aL ,e ta l .C l in i c a ls ign i f i c an c eo f hTERC g en e amp l i f i c a t ion d e t e c t ion b yF ISHinth e s c r e en ing o fc e rv i c a ll e s i o n s .J H u a z h o n gU n i vS c i T e chno l[M edS c i ] ,2009 ,29 (3 ) :3 68 -371 7 Y ang MH ,Y uJ , Ch en N ,e ta l .E l ev a t ed m i c roRNA -31 exp r e s s ionr egu l a t e s co lo r e c t a lc an c e rp rog r e s s ion b y r ep r e s s ing i t st a r g e t g en e SA TB2 . PLoS On e , 2013 ,8 (12 ) : e853 53 8 B en G a c em R ,B en Abd e lk r im O ,Z i ad iS ,e ta l. M e th y l a t ion o f m iR -124 a 1 , m iR -124 a 2 , and m iR -124 a -3 g en e s co r r e l a t e s w i th agg r e s s iv e and adv an c ed b r e a s tc an c e rd i s e a s e .T um o u rB i o l ,2 0 1 3 , [PM ID :24375250 ] 9 G i l ab e r t -E s t e l l e sJ ,B r a z a -Bo i l sA ,R am onLA ,e ta l . Ro l e o fm i c roRNA sin g yn e co log i c a lp a tho log y . Cu r r M ed Ch em ,2012 ,19 ( 15 ) :2406 -2413 10 Zh angX ,M aoH ,LvZ .M i c roRNAro l einth y r o idc an c e r p a thog en e s i s .F ron tB io s c i(L andm a rk Ed ) . 2013 ,18 : 734 -739 11 Hu ang Y ,Sh en X J ,Zou Q,e ta l .B io log i c a lfun c t ion so f m i c r oRNA s : ar e v i ew .J P h y s i o l B i o ch em ,2 0 1 1 , 67 (1 ) :129 -139 12 Y angC , HouC ,Zh ang H ,e ta l .m iR -126fun c t ion sa sa tumo rsupp r e s so rino s t eo s a r com ab yt a r g e t ingSo x2 .In tJ

21 2 Mo lS c i ,2013 ,1 5 (1 ) :423 -437 13 P enn a t i M , Lo p e r go lo A ,P ro fumo V ,e ta l .m iR -205 imp a i r s th e au toph ag i cf lux and enh an c e sc i sp l a t in c y to tox i c i t yinc a s t r a t ion r e s i s t a n tp ro s t a t ec an c e rc e l l s . B io ch emPh a rm a co l ,2014 ,87 (4 ) :579 -597 14 W ang Z , Zh an gH , Zh ang P , e ta l . Up r egu l a t ion o f m iR -2861and m iR -451exp r e s s ioninp ap i l l a r yth y ro id c a r c inom aw i thl ym ph nod e m e t a s t a s i s . M e d On co l , 2013 ,30 (2 ) :577 15 D e n gY ,H u a n gZ ,X uY ,e ta l .M iR -215 modu l a t e sg a s t r i c c an c e rc e l lp ro l i f e r a t ionb yt a r g e t ing RB1 .C an c e rL e t t , 2014 ,342 (1 ) :27 35 16 G eo r g e s SA ,B i e r y MC ,K im SY ,e ta l .Co o rd in a t ed r egu l a t ion o fc e l l cy c l et r an s c r ip t sb y p53 indu c ib l e m i c roRNA s ,m iR -192and m iR -215 .C an c e rR e s ,2008 , 68 (24 ) :10105 -10 1 12 17 K a r a ayv a z M , Zh ang C ,L i an gS ,e ta l .P r o g n o s t i c s ign i f i c an c eo fm iR -205inendo m e t r i a lc a n c e r .PLoSO n e , 2012 ,7 (4 ) : e3515 8 18 H in tonJ ,C a l l anR ,Bod in eC ,e ta l .Po t en t i a lep ig en e t i c b iom a rk e r sfo rth ed i agno s i san dp rogno s i so fp an c r e a t i c du c t a l ad eno c a r c inom a s . Exp e r t R ev Mo l D i agn , 2013 ,13 (5 ) :431 443 19 Co r t inov i s D , Mon i c a V , P i e t r an ton io F , e t a l . M i c roRNA sinnon sm a l lc e l llungc an c e r :cu r r en ts t a tu s andfu tu r eth e r ap eu t i cp rom i s e s . Cu r rPh a rm D e s ,2013 , [PM ID :24138721 ] 20 T ok a r zP ,B l a s i akJ .Th ero l eo fm i c roRNAin m e t a s t a t i c co lo r e c t a lc an c e randi t ss ign i f i c an c einc an c e rp rogno s i s andt r e a tm en t .A c t ab io ch i m i c a Po lon i c a , 20 12 ,59 (4 ) : 467 -474 21 Kh e l l a HW ,B ak h e tM ,A l lo G ,e ta l .m iR -192 ,m iR -194 and m iR -215 : a conv e r g en t m i c roRNA n e two rk supp r e s s ingtumo rp rog r e s s ioninr en a lc e l lc a r c inom a .

JH u a z hongU n ivS c iT e c hno l [M e dS c i] 34 (2 ) :2 01 4

C a r c inog en e s i s ,2013 ,34 (10 ) :223 1 -2239 22 Bon iV ,B i t a r t eN ,C r i s tob a lI ,e ta l .m iR 1 9 2 /m iR 2 1 5 in f lu en c e 5 f l uo rou r a c i l r e s i s t an c e th roug h c e l l c y c l e -m ed i a t ed m e ch an i sm s com p l em en t a r yt oi t s po s t t r an s c r ip t io n a lth ym id i l a t es yn th a s er egu l a t ion . Mo l C an c e rTh e r ,20 10 ,9 (8 ) :2265 -22 75 23 B r aun C J ,Zh an gX ,S av e ly ev aI ,e ta l .p53 -R e spon s iv e m i c ro rn a s192and215a r ec ap ab l eo findu c ingc e l lcy c l e a r r e s t .C an c e rR e s ,2008 ,68 (24 ) :10094 -10104 24 W i jnhov enBP , Hu s s ey D J ,W a t son D I ,e ta l .M i c roRNA p ro f i l ing o f B a r r e t t ’ so e s oph agu s and o e s oph ag e a l ad eno c a r c inom a .B rJSu r g ,201 0 ,97 (6 ) :853 -861 25 K a r a a yv a z M , P a l T , S o n g B , e ta l .P rogno s t i c s ign i f i c an c eo fm iR -215inco lo nc an c e r .C l inC o lo r e c t a l C an c e r ,201 1 ,10 (4 ) :340 -347 26 D e n gY ,H u a n gZ ,X uY ,e ta l .M iR -215 modu l a t e sg a s t r i c c an c e rc e l lp ro l i f e r a t ionb yt a r g e t ing RB1 .C an c e rL e t t , 2014 ,342 (1 ) :27 35 27 W a l t e r BA ,V a l e r a VA ,P in toPA ,e ta l . Comp r eh en s iv e m i c roRNA p ro f i l ing o fp ro s t a t ec an c e r .J C an c e r , 2013 ,4 (5 ) :350 -3 57 28 M a r i s aL ,d eR e yni e sA ,D u v a lA ,e ta l .G en eexp r e s s ion c l a s s i f i c a t iono fco lonc an c e ri n to m o l e cu l a rs ub t yp e s : ch a r a c t e r i z a t ion ,v a l id a t ion ,andp rogno s t i cv a lu e .PLoS M ed ,2013 ,10 (5 ) : e1001453 29 K e l l ey RK , V enook AP .P r ogno s t i c and p r ed i c t iv e m a r k e r si ns t ag e Ⅱ co lonc an c e r :i sth e r earo l ef o rg en e exp r e s s ion p r o f i l ing ? C l in Co lo r e c t a l C an c e r , 201 1 ,10 (2 ) :73 -8 0 30 Zh angJX ,S on g W , Ch en ZH ,e ta l .P rogno s t i cand p r ed i c t iv ev a lu eo fa m i c roRNAs ign a tu r eins t ag eI I co lonc an c e r :a m i c roRNAexp r e s s ionan a l y s i s .L an c e t On co l ,2013 ,14 ( 13 ) :1295 -1306 (R e c e iv edD e c .8 ,2013 ;r ev i s edF eb .20 ,2014 )

MicroRNA-215 is a potential prognostic marker for cervical cancer.

Recently, microRNAs (miRNAs) have been shown to be involved in multiple biological pathways that can influence tumor progression and metastasis and th...
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