The search for interacting long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs of protein-coding genes through the mechanism of competing endogenous RNAs in tumors of ovarian cancer ...patients was carried out. The levels of expression of 24 lncRNAs, 20 miRNAs, and 28 mRNAs of protein-coding genes involved in oncogenesis were determined by real-time PCR on a set of representative samples. Correlations between lncRNAs/miRNA and miRNA/mRNA levels in ovarian cancer samples were analyzed. We identified 8 pairs of lncRNAs/miRNA and 17 pairs of miRNA/mRNA, the expression levels of which have a negative correlation. Five triplets of potentially interacting lncRNAs/miRNA/mRNA have been identified, among which the most significant triplet is the
OIP5
-
AS1
/
miR-203a-3p
/
ZEB1
. The data obtained determine new epigenetic profiles, as well as new potential biomarkers and targets for targeted therapy of ovarian cancer patients.
Late diagnosis of ovarian cancer is one of the most important problems in its treatment. Long non-coding RNA (lncRNA) are a poorly studied, but promising type of diagnostic biomarkers. We studied the ...lncRNA interactome to identify biomarkers with potential significance for molecular diagnostics of ovarian cancer. By screening the TCGA database, we identified differentially expressed lncRNA CCAT1 and SNHG14. Based on the indices of complementarity of CCAT1 and SNHG14 to the mRNA sequences, we selected 5 protein-coding genes
MAPK1
,
c-MET
,
TGFB2
,
SNAIL1
, and
WNT4
associated with the epithelial-mesenchymal transition. Real-time PCR on 54 ovarian cancer samples confirmed the high expression levels of CCAT1 and SNHG14 (logFC>1.5,
p
<0.05). A positive correlation between the expression levels of two lncRNA and mRNA of 5 genes in 6 pairs was established. The activating effect of CCAT1 and SNHG14 on the expression of these genes can be mediated by miR-203 and miR-124.
Ovarian cancer (OC) develops asymptomatically and escapes diagnosis until advanced stages, the feature contributing to a higher mortality rate. New prospects of OC diagnosis and treatment have been ...opened in studies of the gene regulation mechanisms that involve long noncoding RNAs (lncRNAs) and identification of the lncRNA genes that are inhibited via methylation of the promoter region. A set of 122 samples of primary OC tumors was examined by methylation specific real-time PCR to assess the methylation level of the lncRNA genes
PLUT
,
SNHG1
,
SNHG6
,
SNHG12,
and
TINCR
. A significant increase in their methylation levels was observed in OC (
p
< 0.001 by the nonparametric Mann–Whitney test). The methylation levels of
SNHG6
,
SNHG12
, and
TINCR
were found to correlate significantly (
p
< 0.05) with the stage of the tumor process, the histological grade, and metastasis. Downregulation of
SNHG6
,
SNHG12
, and
TINCR
was detected by real-time RT–qPCR, and a significant correlation between methylation and expression was demonstrated for
SNHG6
and
TINCR
(
r
s
≤ –0.5,
p
< 0.001). The respective lncRNA genes were assumed to provide potential epigenetic markers of OC.
Introduction.
Multiple primary malignant neoplasms of female reproductive organs are a rare pathology. However, over the past decades, there has been an upsurge of interest in the study of this ...phenomenon in oncology. This is particularly the case for the diagnosis of synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus, which histogenetically belong to the same germ layer and have similar histological structure. Until recently, clinicians relied only on morphological examination in these cases, but with the development of molecular genetic technologies, new diagnostic possibilities have emerged.
Aim.
Is the detection of the status of microsatellite instability in tumors of patients with endometrioid adenocarcinoma of the ovaries and/or uterine corpus.
Materials and Methods.
A pilot retrospective molecular genetic study (
n
= 48) was conducted to determine the status of microsatellite instability (MSI) in the tumors of the ovaries and/or uterine corpus: it involved 33 patients with solitary endometrioid ovarian cancer and 15 patients with synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus. Microsatellite instability status was detected using PCR method with subsequent fragment analysis performed on ABI PRISM 3500 genetic analyzer (8 capillaries, Applied Biosystems). DNA was isolated from paraffin blocks of surgical specimens using DNAsorb B extraction kit (AmpliSens, Russia), according to the manufacturer’s manual. DNA concentration was estimated fluorometrically using Qubit 2.0 (Life Technologies, USA). The obtained data were analyzed using GeneMapper program (Thermo Fisher, USA). In case of polymorphism of two and more markers high-level microsatellite instability (MSI-H) was observed.
Results.
The incidence of MSI-H in solitary endometrioid ovarian cancer (
n
= 33) was 12,1 % (4 cases), while in synchronous ovarian and uterine corpus tumors (
n
= 15) MSI-H incidence made up 20 % (
n
= 3). Herewith, there have been only cases of a combination of endometrioid histotypes of ovarian and endometrial cancer with identical status of microsatellite instability. Thus, the incidence of MSI-H in synchronous endometrioid adenocarcinoma of the ovaries and uterine corpus (20 %) is comparable to that in solitary endometrial cancer.
Conclusion.
Our pilot study became a significant complement to the previously published materials, as it allowed to confirm the clonal origin of tumors in patients with endometrioid adenocarcinoma of the ovaries and uterine corpus, that can affect the stratification of treatment strategy for this category of patients.
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