Abstract
AbstractProlactinomas are the most frequently observed pituitary adenomas (PAs), and 5%–18% tumors were resistant to the dopamine agonists (DAs). MicroRNAs (miRNAs) dysfunction play a key role in tumorigenesis. Agilent miRNA and an expression chip were used for six prolactinomas and three normal pituitary specimens. Differentially expressed genes were confirmed by RT-qPCR. The level of DDR1 and SAT1 was determined with tissue micro-array (TMA) and western blot. A MMQ cell line was used for functional experiments. We have identified 5-miRNA and 12 target gene signatures of prolactinomas through gene ontology analysis. miRNA-199a-5p was selected for experiments that integrated the results from prolactinomas specimens and a rat prolactinoma model induced by 17-b-estradiol. Tumors with low miRNA-199a-5p had a significantly invasive behavior and a higher tumor volume (p<0.05). DDR1 and SAT1, target genes of miRNA-199a-5p, had higher H-scores in the invasive group than those of the non-invasive group through TMA. An overexpression of miRNA-119a-5p suppressed the PRL secretion and the cell viability through upregulated the apoptosis level in MMQ cells (p<0.01). Furthermore, we found the target genes expression of DDR1 and SAT1 were affected by miRNA-199a-5p regardless of mRNA levels or protein levels. This study provided evidence that downregulation of miRNA-199a-5p may contribute to prolactinoma tumorigenesis.
Highlights
Expressed genes were confirmed by RT-qPCR.The level of DDR1 and spermine N1-acetyltransferase 1 (SAT1) was determined with tissue 1 Introduction micro-array (TMA) and western blot
We found numerous deregulated miRNAs in prolactinomas, and confirmed changes in five miRNAs and 12 target genes at the mRNA level
Functional studies showed that miRNA-199a-5p inhibited cell proliferation and activated the apoptosis in the MMQ cell line, suggesting a critical role in prolactinomas tumorigenesis
Summary
The level of DDR1 and SAT1 was determined with tissue 1 Introduction micro-array (TMA) and western blot. We hapveaiirdAen,tAif∗iedof dPiaitguoitnaarylizaadbelneoFm-alisne(PaArsm) aarpestohne Vse,ceoancdhmoofswt hcoicmhmaocnts on an eige 5-miRNA and 12 target gene signatures of priorrleadctuincoibmleastridiniatgraocnraanl ifaalshtuiomno.rSsu, cahnad ppariorliascctianlolemdasa Laereontahred pmaoisrt(see [13, De tspherrloeolcautcgethdinfogomernaeesxpsoeprneitcmoimleonegtnyssthaanantadliynastiersag.trampteriodRlNathcAte-i1sAn9rwoe,9msaAaup-a∗5lstpsmisAforwsaodaanmeisdld tAocD[∗1obA].m.esI.nGmsDuetoAhlindfsi-esdsaluciurnaeabeslttsyehwpessheuuf.egicrngMhseetosavcstnehtrtoahptiuarchoetteolarttmorecetoteairnxrtemopiasmhtetnisahstsyampnwreeiirasstphpuurdotononrlaiamdqwcuotawiernlep,elmhaml niatisoaydmcoaflltehdetehnedd induced by 17-b-estradiol. DDR1 and SAT1, tarLgeeot ngaenrdespaofir o5f -K18r%awptcrholoauctkintyopmea(ssedeo[1n0o,t Dreespnointidonto6.t1h]e); (triieia)ttmheenLte, onard pair a miRNA-199a-5p, had higher H-scores in the inmvaosdivuelgerfoourptheeTvernwaitllhigigehr adlogseebsraofoDf Aasd[i3s]t.aTnhce-mreagiunlashr ogrrtacpomh itnhgatohf as a spin m than those of the non-invasive group throubgrhaT(sMeAe.[A1,nTheDoArsemis],th[3e, Tlohnego-treermsm4e.1d,i5ca.5t]io);n(icvo)manpaarepdprtoopsriuartgeelryy.normalized overexpression of miRNA-119a-5p suppress(esdeet[h1e1, PLReLmmCaa1b4e.r8g]o);li(nve)isthgeenLeeroanllyarfadvporaeidr acos tnhseistrteinagtmoefnatnoyf cthwooicoe,f a modular secretion and the cell viability through uprDegeulnatietidonth1e.4])a;lt(hvoi)utghhethLiesodnraurgdmpaayirhcaovnestihsteinsagmoef ainpcraeiarsoedf orpispkoosfite generato apoptosis level in MMQ cells (p
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
