TY  - JOUR
A1  - Wünsch, Anna Chiara
A1  - Ries, Elena
A1  - Heinzelmann, Sina
A1  - Frabschka, Andrea
A1  - Wagner, Peter Christoph
A1  - Rauch, Theresa
A1  - Koderer, Corinna
A1  - El-Mesery, Mohamed
A1  - Volland, Julian Manuel
A1  - Kübler, Alexander Christian
A1  - Hartmann, Stefan
A1  - Seher, Axel
T1  - Metabolic silencing via methionine-based amino acid restriction in head and neck cancer
JF  - Current Issues in Molecular Biology
N2  - In recent years, various forms of caloric restriction (CR) and amino acid or protein restriction (AAR or PR) have shown not only success in preventing age-associated diseases, such as type II diabetes and cardiovascular diseases, but also potential for cancer therapy. These strategies not only reprogram metabolism to low-energy metabolism (LEM), which is disadvantageous for neoplastic cells, but also significantly inhibit proliferation. Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumour types, with over 600,000 new cases diagnosed annually worldwide. With a 5-year survival rate of approximately 55%, the poor prognosis has not improved despite extensive research and new adjuvant therapies. Therefore, for the first time, we analysed the potential of methionine restriction (MetR) in selected HNSCC cell lines. We investigated the influence of MetR on cell proliferation and vitality, the compensation for MetR by homocysteine, the gene regulation of different amino acid transporters, and the influence of cisplatin on cell proliferation in different HNSCC cell lines.
KW  - amino acid restriction
KW  - caloric restriction
KW  - methionine
KW  - HNSCC
KW  - SCCHN
KW  - cisplatin
KW  - amino acid transporter
KW  - SLC-family
KW  - cell vitality
KW  - low energy metabolism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-319257
SN  - 1467-3045
VL  - 45
IS  - 6
SP  - 4557
EP  - 4573
ER  - 
TY  - JOUR
A1  - Steiner, Thomas
A1  - Zachary, Marie
A1  - Bauer, Susanne
A1  - Müller, Martin J.
A1  - Krischke, Markus
A1  - Radziej, Sandra
A1  - Klepsch, Maximilian
A1  - Huettel, Bruno
A1  - Eisenreich, Wolfgang
A1  - Rudel, Thomas
A1  - Beier, Dagmar
T1  - Central Role of Sibling Small RNAs NgncR_162 and NgncR_163 in Main Metabolic Pathways of Neisseria gonorrhoeae
JF  - mBio
N2  - Small bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in a very few cases has the role in metabolism been demonstrated. Here, we performed a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 (NgncR_162/163) and their impact on the metabolism of Neisseria gonorrhoeae. These sRNAs have been reported to control genes of the citric acid and methylcitric acid cycles by posttranscriptional negative regulation. By transcriptome analysis, we now expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially in the uptake of glycine, phenylalanine, and branched-chain amino acids. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and, hence, probably affect biosyntheses of nucleotides, vitamins, and other amino acids via the supply of one-carbon (C\(_1\)) units. Indeed, these roles were confirmed by metabolomics and metabolic flux analysis, which revealed a bipartite metabolic network with glucose degradation for the supply of anabolic pathways and the usage of amino acids via the citric acid cycle for energy metabolism. Thus, by combined deep RNA sequencing (RNA-seq) and metabolomics, we significantly extended the regulon of NgncR_162/163 and demonstrated the role of NgncR_162/163 in the regulation of central metabolic pathways of the gonococcus.
KW  - sRNA
KW  - Neisseria gonorrhoeae
KW  - posttranscriptional regulation
KW  - amino acid transporter
KW  - bipartite metabolism
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313323
VL  - 14
ER  -