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Towards an enhanced understanding of osteoanabolic effects of PTH-induced microRNAs on osteoblasts using a bioinformatic approach
ID
Vrščaj, Lucija Ana
(
Avtor
),
ID
Marc, Janja
(
Avtor
),
ID
Ostanek, Barbara
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(4,27 MB)
MD5: 24ED8222BEA387D6E25FA58DE04FF72B
URL - Izvorni URL, za dostop obiščite
https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1380013/full
Galerija slik
Izvleček
In this study, we used a bioinformatic approach to construct a miRNA-target gene interaction network potentially involved in the anabolic effect of parathyroid hormone analogue teriparatide [PTH (1–34)] on osteoblasts. We extracted a dataset of 26 microRNAs (miRNAs) from previously published studies and predicted miRNA target interactions (MTIs) using four software tools: DIANA, miRWalk, miRDB, and TargetScan. By constructing an interactome of PTH-regulated miRNAs and their predicted target genes, we elucidated signaling pathways regulating pluripotency of stem cells, the Hippo signaling pathway, and the TGF-beta signaling pathway as the most significant pathways in the effects of PTH on osteoblasts. Furthermore, we constructed intersection of MTI networks for these three pathways and added validated interactions. There are 8 genes present in all three selected pathways and a set of 18 miRNAs are predicted to target these genes, according to literature data. The most important genes in all three pathways were BMPR1A, BMPR2 and SMAD2 having the most interactions with miRNAs. Among these miRNAs, only miR-146a-5p and miR-346 have validated interactions in these pathways and were shown to be important regulators of these pathways. In addition, we also propose miR-551b-5p and miR-338–5p for further experimental validation, as they have been predicted to target important genes in these pathways but none of their target interactions have yet been verified. Our wet-lab experiment on miRNAs differentially expressed between PTH (1–34) treated and untreated mesenchymal stem cells supports miR-186–5p from the literature obtained data as another prominent miRNA. The meticulous selection of miRNAs outlined will significantly support and guide future research aimed at discovering and understanding the crucial pathways of osteoanabolic PTH-epigenetic effects on osteoblasts. Additionally, they hold potential for the discovery of new PTH target genes, innovative biomarkers for the effectiveness and safety of osteoporosis-affected treatment, as well as novel therapeutic targets.
Jezik:
Angleški jezik
Ključne besede:
osteoporosis
,
miRNA
,
signaling pathways
,
Hippo signaling pathway
,
TGF- β signaling pathway
,
signaling pathways
,
regulating pluripotency of stem cells
,
osteoblasts
Vrsta gradiva:
Članek v reviji
Tipologija:
1.01 - Izvirni znanstveni članek
Organizacija:
FFA - Fakulteta za farmacijo
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2024
Št. strani:
15 str.
Številčenje:
Vol. 15, [article no.] 1380013
PID:
20.500.12556/RUL-160980-5ebeae6a-2440-101b-e8df-d99282a8c79c
UDK:
616.71-007.234
ISSN pri članku:
1664-2392
DOI:
10.3389/fendo.2024.1380013
COBISS.SI-ID:
203698435
Datum objave v RUL:
06.09.2024
Število ogledov:
55
Število prenosov:
24
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Objavi na:
Gradivo je del revije
Naslov:
Frontiers in endocrinology
Založnik:
Frontiers Research Foundation
ISSN:
1664-2392
COBISS.SI-ID:
3340154
Licence
Licenca:
CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
Povezava:
http://creativecommons.org/licenses/by/4.0/deed.sl
Opis:
To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
miRNA
,
signalne poti
,
signalna pot Hippo
,
signalizacija TGF-β
,
pluripotenca matičnih celic
,
osteoblasti
,
lipaze
,
osteoporoza
Projekti
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
P3-0298
Naslov:
Geni, hormonske in osebnostne spremembe pri metabolnih motnjah
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
J3-1759
Naslov:
Celostna karakterizacija zadetkov analiz GWAS - pot do novih terapevtskih tarč za anabolno zdravljenje osteoporoze (GWASforAna)
Financer:
ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
Številka projekta:
J3-4527
Naslov:
Mišični sekretom in kostne celice - sodelovanje pri osteosarkopeniji (MiKOSA)
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
Young Research Program
Številka projekta:
53726
Financer:
Drugi - Drug financer ali več financerjev
Program financ.:
GEMSTONE COST-Action
Številka projekta:
CA18139
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