TY  - JOUR
A1  - Kunz, Meik
A1  - Göttlich, Claudia
A1  - Walles, Thorsten
A1  - Nietzer, Sarah
A1  - Dandekar, Gudrun
A1  - Dandekar, Thomas
T1  - MicroRNA-21 versus microRNA-34: Lung cancer promoting and inhibitory microRNAs analysed in silico and in vitro and their clinical impact
JF  - Tumor Biology
N2  - MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.
KW  - biomarker
KW  - microRNA–target interaction
KW  - microRNAs
KW  - lung cancer
KW  - therapeutic strategy
KW  - bioinformatics
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158399
VL  - 39
IS  - 7
ER  - 
TY  - JOUR
A1  - Jazbutyte, Virginija
A1  - Fiedler, Jan
A1  - Kneitz, Susanne
A1  - Galuppo, Paolo
A1  - Just, Annette
A1  - Holzmann, Angelika
A1  - Bauersachs, Johann
A1  - Thum, Thomas
T1  - MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart
JF  - AGE
N2  - MicroRNAs (miRs) are small non- coding RNA molecules controlling a plethora of biological processes such as development, cellular survival and senescence. We here determined miRs differentially regulated during cardiac postnatal development and aging. Cardiac function, morphology and miR expression profiles were determined in neonatal, 4 weeks, 6 months and 19 months old normotensive male healthy C57/Bl6N mice. MiR-22 was most prominently upregulated during cardiac aging. Cardiac expression of its bioinformatically predicted target mimecan (osteoglycin, OGN) was gradually decreased with advanced age. Luciferase reporter assays validated mimecan as a bona fide miR-22 target. Both, miR-22 and its target mimecan were co- expressed in cardiac fibroblasts and smooth muscle cells. Functionally, miR-22 overexpression induced cellular senescence and promoted migratory activity of cardiac fibroblasts. Small interference RNA-mediated silencing of mimecan in cardiac fibroblasts mimicked the miR-22-mediated effects. Rescue experiments revealed that the effects of miR-22 on cardiac fibroblasts were only partially mediated by mimecan. In conclusion, miR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity. Our results suggest an involvement of miR-22 in age-associated cardiac changes, such as cardiac fibrosis.
KW  - cardiac fibrosis
KW  - cardiac aging
KW  - microRNAs
KW  - miR-22
KW  - mimecan
KW  - osteoglycin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126745
VL  - 35
IS  - 3
ER  -