Science News - August 28, 2010

Network in healthy lungs
Network breakdown in lung tumors

Going rogue the networks through which micrornas (colored boxes) indirectly regulate each other can break down in cancer. in healthy lung tissue (left), researchers found a complete microrna network, but cancerous tissue possessed one main network along with eight subnetworks (right).

micro RNAs, which occur at high levels in
somecancercells,latchontomessenger
RNAsencodingDicerandratchetdown
its production, meaning less of other
micro RNAsgetmade.ButDicerlevels
neverdroptonothing,becausethesame
microRNAsrelyontheproteintosnip
themfreefromlargerpiecesofRNA.
Piccolo’s finding neatly solves the
paradoxof whymostmicroRNAlevels
canbelowincancercellswhilesomeare
high,buthisstudydidn’tstopthere.The
researchalsoprovidesfurtherevidence
thatlowDicerlevelsmakecancermore
dangerous.
In the study, Piccolo’s team discov
eredthat some aggressive tumors had
higherthannormallevelsofthemicro
RNAsthatregulateDicer, andthusless
oftheprotein. Moreofthesemicro RNAs
werealsoassociatedwithbreastcancer’s
spreadandpoorprognosisinpatients.
Tumorcellsmaybetakingadvantageof
oneofDicer’sjobsinnormalcells—help
ingcellsmovearound. “Cancerdoesn’t
inventanything,”Piccolosays.

Tiny treatment options

Getting a clue that a microRNA is involved in a problem also gives researchers a potential solution. In experimentswithmice,inhibitingmiR- 21maderesistanttumorcellsmoresus ceptibletoHerceptin,Rehmanreported atthecancerresearchmeeting.

Increasing susceptibility to anti cancerdrugsisjustonewaythatmicro RNAscouldbeusefulintheclinic,says oncologistMullerFabbriofOhioState.

SpecificmicroRNAlevelsriseorfall in different tumor types, creating a signatureforthattypeofcancer,stud ieshaveshown.Suchsignaturescould helpcorrectlydiagnosecancerinpeo plewhosetumorshavemigrated.Often pathologistscanexamineabraintumor anddeterminethatitarosefrombreast cancercells,butsometimescancercells concealtheirrealbirthplace.Character isticpatternsofmicroRNAcouldhelp

Levels by organ microrna levels that are too high for one organ may be just right for another. healthy brain cells, for example, have fewer copies of mir-21 molecules than healthy cells in the last portion of the colon.

miR-21 copies in different cell types

25,000

Blad der H eart

20,000

Copies
B rain

15,000

Distal C olo n

10,000

Lung
source: liang et al/Bmc genomics 2007
0

5,000

Pancreas

identifywheretumorcellsoriginatedin
the 8to 10percentofcaseswhen“even
the pathologist doesn’t have a clue,”
Fabbrisays.Examiningthepatternof
microRNAlevelsin apatient’stumor
mayalsohelpdoctorsidentifyaggres
siveforms(SN: 2/2/08, p. 70).
In diseases such as liver cancer,
researchers may be able to replace
missingmicroRNAsorboostlevelsto
stop thecancer, ateamreported last
yearinCell.Andincancersinwhichlev
elsofcertainmicro RNAsaretoohigh,
researcherscandeploydecoymolecules
topullmicro RNAsfromtheirtargets.
AteamreportedinJanuaryin Science
thatthestrategyappearsto workfor
treatinghepatitisCinfectioninmon
keys(SN: 1/2/10, p. 14).

Croce thinks that targeting several
microRNAsinanarchistnetworksmay
helptreatcancer withlittle chanceof
resistancedeveloping. Butsuchthera
pies are still years away. “ We have to
showthatitisreallytrue,”hesays,“not
just in experiments with mice, but in
clinicaltrials.”
Fornow,nomicroRNAtherapiesare
availableforcancer,butresearchersare
watching trials of the antimicroRNA
therapyagainsthepatitisCinpeople.

“The rapidity of what’s going on is what gives some of us optimism that thiscouldhavevalue,”Harrissays.“Rel ativelyshortly,we’regoingtoknowthe degreeofimportanceofmicroRNAs.”