Small non-coding RNAs (
sncRNAs) represent a heterogeneous group of <200nt-long transcripts comprising
microRNAs, PIWI-interacting RNAs (
piRNAs) and small-nucleolar-RNAs (snoRNAs) involved in physiological and
pathological processes such as
carcinogenesis and
tumor progression. Aberrant
sncRNA expression in
cancer has been associated with specific clinical phenotypes, grading, staging,
metastases development and resistance to
therapy.Aim of the present work is to study the role of
sncRNAs in endometrial
carcinogenesis. Changes in
sncRNA expression were identified by high-throughput genomic analysis of paired normal, hyperplastic and cancerous endometrial tissues obtained by endometrial biopsies (n = 10). Using smallRNA sequencing and microarrays we identified significant differences in
sncRNA expression pattern between normal, hyperplastic and neoplastic endometrium. This led to the definition of a
sncRNA signature (129
microRNAs, 2 of which not previously described, 10
piRNAs and 3 snoRNAs) of neoplastic transformation. Functional bioinformatics analysis identified as downstream targets multiple signaling pathways potentially involved in the hyperplastic and neoplastic tissue responses, including Wnt/β-
catenin, and ERK/MAPK and TGF-β-Signaling.Considering the regulatory role of
sncRNAs, this newly identified
sncRNA signature is likely to reflect the events leading to
endometrial cancer, which can be exploited to dissect the carcinogenic process including novel
biomarkers for early and non-invasive diagnosis of these
tumors.