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  - Kunz, Meik
A1  - Wolf, Beat
A1  - Schulze, Harald
A1  - Atlan, David
A1  - Walles, Thorsten
A1  - Walles, Heike
A1  - Dandekar, Thomas
T1  - Non-Coding RNAs in Lung Cancer: Contribution of Bioinformatics Analysis to the Development of Non-Invasive Diagnostic Tools
JF  - Genes
N2  - Lung cancer is currently the leading cause of cancer related mortality due to late diagnosis and limited treatment intervention. Non-coding RNAs are not translated into proteins and have emerged as fundamental regulators of gene expression. Recent studies reported that microRNAs and long non-coding RNAs are involved in lung cancer development and progression. Moreover, they appear as new promising non-invasive biomarkers for early lung cancer diagnosis. Here, we highlight their potential as biomarker in lung cancer and present how bioinformatics can contribute to the development of non-invasive diagnostic tools. For this, we discuss several bioinformatics algorithms and software tools for a comprehensive understanding and functional characterization of microRNAs and long non-coding RNAs.
KW  - lung cancer
KW  - non-invasive biomarkers
KW  - miRNAs
KW  - lncRNAs
KW  - bioinformatics
KW  - early diagnosis
KW  - algorithm
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147990
VL  - 8
IS  - 1
ER  - 
TY  - JOUR
A1  - Stojanović, Stevan D.
A1  - Fuchs, Maximilian
A1  - Fiedler, Jan
A1  - Xiao, Ke
A1  - Meinecke, Anna
A1  - Just, Annette
A1  - Pich, Andreas
A1  - Thum, Thomas
A1  - Kunz, Meik
T1  - Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts
JF  - International Journal of Molecular Sciences
N2  - Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.
KW  - bioinformatics
KW  - miR
KW  - proteomics
KW  - functional network analysis
KW  - senescence
KW  - lung fibrosis
KW  - autophagy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285181
SN  - 1422-0067
VL  - 21
IS  - 11
ER  -