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Vpletenost s paratiroidnim hormonom uravnavanih miRNA v signalni poti Wnt in RANK/RANKL/OPG = Involvement of parathyroid hormone-regulated miRNAs in the Wnt and RANK/RANKL/OPG signalling : magistrska naloga : enoviti magistrski študijski program FarmacijaEmkić, ErmaKostna prenova je usklajeni proces kostne razgradnje in izgradnje. V njej igrata pomembno vlogo signalna pot Wnt in signalna pot RANK/RANKL/OPG. Parathormon (PTH) vpliva tako na kostno razgradnjo kot ... na izgradnjo. V primeru intermitentne izpostavljenosti pride do povečanja kostne mase, zato v terapiji osteoporoze uporabljamo njegovo rekombinantno obliko (teriparatid) kot osteoanabolno zdravilo. Eden od mehanizmov vpliva PTH na kosti je preko sprememb izražanja mikro RNA (miRNA). Le-te predstavljajo kratke, nekodirajoče RNA, ki zavirajo izražanje genov po transkripciji. Namen magistrske naloge je bil ugotoviti, katerim miRNA, ki uravnavajo izražanje genov v signalni poti Wnt ali RANK/RANKL/OPG, se spremeni izražanje pod vplivom PTH. V elektronski knjižnici PubMed smo pregledali literaturo, nato s pomočjo bioinformatičnih orodij DIANA tools, miRWalk, TargetScan ter miRDB naredili napovedi tarčnih genov za izbrane miRNA, z bioinformatičnim orodjem miRTarBase preverili eksperimentalno potrjene interakcije ter izrisali interaktome z orodjem Cytoscape. S pregledom literature smo zbrali 17 relevantnih člankov, iz katerih smo pridobili nabor 69 miRNA, za katere smo naredili napovedi. Skupno število vseh potencialnih tarčnih genov je bilo 12782, eksperimentalno potrjenih pa 477. V nadaljevanju smo analizirali miRNA, ki vplivajo na signalno pot Wnt in signalno pot RANK/RANKL/OPG, ločeno ali na obe hkrati. MiRNA, ki vpliva na obe signalni poti, lahko predstavlja obetavno potencialno zdravilo, v kolikor so njeni učinki tišanja ustrezni, torej da deluje hkrati osteanabolno in antiresorptivno. Kot potencialno zdravilo za zdravljenje osteoporoze bi lahko uporabili miRNA hsa-miR-24-2-5p, katere izražanje v kostnih celicah bi bilo potrebno v nadaljnjih študijah izmeriti. Naši rezultati potrjujejo pomemben vpliv miRNA na obe signalni poti in predstavljajo izhodišče za nove zdravilne učinkovine v terapiji osteoporoze.Type of material - master's thesis ; adult, seriousPublication and manufacture - Ljubljana : [E. Emkić], 2022Language - slovenianCOBISS.SI-ID - 122430211
Author
Emkić, Erma
Other authors
Ostanek, Barbara, 1972- |
Vrščaj, Lucija Ana
Topics
Kostna denzitometrija |
Osteoporoza |
osteoporoza |
PTH |
signalna pot Wnt |
signalna pot RANK/RANKL/OPG |
miRNA |
parathormon |
receptor za aktivacijo jedrnega dejavnika kapa B
Library/institution |
City | Acronym | For loan | Other holdings |
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Faculty of Pharmacy, Ljubljana | Ljubljana | FFALJ |
reading room 1 cop.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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DRS, in which the journal is indexed
Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Emkić, Erma | |
Ostanek, Barbara, 1972- | 18154 |
Vrščaj, Lucija Ana | 53726 |
Source: Personal bibliographies
and: SICRIS
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