PO-155 Therapeutic evaluation of HEDGEHOG-GLI signalling pathway through miRNA and mRNA profiling of ovarian carcinoma

• Published in: ESMO open 2018-07, Vol.3 (Suppl 2), p.A287-A287
• Main Authors: Levanat, S, Ozretic, P, Hackl, H, Plattner, C, Trnski, D, Sabol, M, Kalafatic, D, Musani, V
• Format: Article
• Language: English
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1136/esmoopen-2018-EACR25.677

IntroductionSignalling pathway Hedgehog-Gli (Hh-Gli) is involved in embryonal ovarian development, but its atypical activation can lead to different types of ovarian tumours. Our previous studies showed aberrant Hh-Gli activity in some ovarian tumour types and hypermethylation in a promoter of tumour suppressor gene PTCH1 in the CpG islands near the GLI-binding site (Sabol et al. Int J Oncol 2012, 2017;Musani et al. Gene 2013; Maurac et al. Int J Gynecol Pathol 2012). We and other are aware that various genetic and epigenetic alterations contribute to aberrant Hh-Gli pathway activity in ovarian cancer, which could serve as interesting targets for cancer treatment and therapy, especially if can be used to bypass resistance and to target cancer in more efficient way. We hypothesise that changes in the expression of miRNA molecules related to the Hh-Gli signalling pathway genes contribute to the development of high-grade serous ovarian carcinoma (HGSOC).Material and methodsWe conducted a miRNA profiling of HGSOC and healthy Fallopian tube control samples with Agilent SurePrint G3 Human miRNA 8 × 60K Microarray Kit containing probes for 2549 human miRNAs. Gene expression profiling was preformed using Agilent SurePrint G3 Human Gene Expression v3 8 × 60K Microarray Kit, which covers 37 756 known RefSeq coding transcripts. Data were analysed using R/Bioconductor packages AgiMicroRna and limma. On-line DIANA Tools (TarBase, microT-CDS and miRPath) were used to find which Hh-Gli genes are targets of miRNAs differentially expressed in HGSOC.Results and discussionsData filtration gave 55 miRNAs: 32 up- and 23 down-regulated in HGSOC. Out of 47 genes involved in Hh-Gli pathway in humans (KEGG Pathway hsa04340), 35 are known targets for 27 over-expressed miRNAs, 22 are known targets for 16 under-expressed miRNAs, while 28 genes are potential targets for 26 up-regulated miRNAs and 24 are potential targets for 19 down-regulated miRNAs in HGSOC. In addition, 1090 genes were significantly over-expressed and 1692 were under-expressed in HGSOC. Further analysis revealed a couple of potential combinations of miRNAs and their target genes which are members of Hh-Gli pathway: ADRBK2/hsa-miR-96–5 p, BCL2/hsa-miR-16–5 p and hsa-miR-96–5 p, BOC/hsa-miR-224–5 p, and IHH/hsa-miR-16–5 p, hsa-miR-107 and hsa-miR-103a-3p.ConclusionOur results highlighted several candidate miRNAs targeting Hh-Gli signalling pathway genes, which, when additionally verified, could be potentially used for