TY  - GEN
UR  - https://archiv.ub.uni-heidelberg.de/volltextserver/24522/
A1  - Weiss, Melanie
N2  - Deregulation of promoter methylation is a well-defined phenomenon in prostate cancer (PCa). This does not only lead to the inactivation of tumor suppressors but also to the activation of oncogenes, enabling the acquisition of the hallmarks of cancer. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are involved in DNA methylation and demethylation processes through recruitment of DNA methylation modifiers to specific genomic locations.

Since alterations in DNA methylation of protein-coding genes are associated with prostate carcinogenesis and might be regulated by cis transcribed RNAs, we aimed to identify lncRNAs involved in DNA (de)methylation mechanisms in PCa. By integrating DNA methylation and RNA sequencing data generated by collaborators from the International Cancer Genome Consortium (ICGC) project, we have identified the lncRNA DLX6-AS1 as the potential regulator of the cis protein-coding gene DLX6.

DLX6 and DLX6-AS1 transcript expression is upregulated and significantly correlates in two independent cohorts of PCa patients, as well as in five different cancer entities. In line with elevated expression levels of DLX6/DLX6-AS1, the DLX6 promoter region is hypomethylated in tumor samples. The impact of elevated DLX6/DLX6-AS1 levels on patient?s prognosis varies with the tumor type. The clinical data corroborate our hypothesis that DLX6-AS1 can regulate the cis protein-coding gene DLX6 by decreasing DLX6 promoter DNA methylation. Nevertheless, we showed through loss- and gain-of-function approaches that DLX6-AS1 does not regulate DLX6 at the transcript level by influencing local DNA methylation levels. The sequence features as well as the association to polysomes of the major splice variant of DLX6-AS1 (DLX6-AS1 T1), suggests rather a DLX6 protein synthesis regulatory role for this transcript.

Detailed investigation of the function and expression pattern of all DLX6-AS1 splice variants in different cancer types will help to clarify the link between DLX6/DLX6-AS1 expression and patients? prognosis.
ID  - heidok24522
Y1  - 2018///
TI  - Identification and mechanistic characterization of DLX6-AS1 lncRNA in prostate cancer
AV  - public
KW  - epigenetics
lncRNA
DNA methylation
prostate cancer
ER  -