Structural and functional disruptions of the epigenome are hallmarks of breast and ovarian carcinogenesis. This review dissects the reciprocal regulatory networks co-operated by DNA methyltransferases (DNMTs), ten-eleven translocation enzymes (TETs), and key non-coding RNAs (microRNAs and lncRNAs). We map the precise molecular mechanisms through which these epigenetic modulators alter chromatin accessibility, drive transcriptional reprogramming, and promote phenotypic plasticity in hormone-dependent malignancies. By systematically contrasting the distinct yet overlapping epigenetic profiles of breast and ovarian tumors, we elucidate how these aberrations dictate clinical outcomes. This comprehensive synthesis offers critical insights into the dual utility of these epigenetic elements as dual-purpose diagnostic biomarkers and druggable therapeutic targets, laying the groundwork for next-generation targeted epigenetical therapies.

Breast cancer is the most commonly diagnosed malignancy in women. Despite advances in diagnostics and treatment, the key molecular mechanisms underlying its development remain incompletely understood. This study aimed to identify novel lncRNA–miRNA–mRNA regulatory networks potentially involved in breast cancer–associated signaling pathways. Using an RT² lncRNA PCR Array and bioinformatic analysis, we identified seven differentially expressed (DE) lncRNAs. Four of these—ADAMTS9-AS2, HAND2-AS1, HOTAIRM1, and MEG3—were prioritized through integrative evaluation. qPCR confirmed their downregulation and aberrant methylation in breast tumor samples. We observed significant positive expression correlations between the pairs ADAMTS9-AS2–MEG3, HAND2-AS1–MEG3, and HOTAIRM1–MEG3, as well as co-methylation among ADAMTS9-AS2–HAND2-AS1, ADAMTS9-AS2–HOTAIRM1, HAND2-AS1–MEG3, and HAND2-AS1–HOTAIRM1, suggesting coordinated regulation. These findings are consistent with data from GEPIA 2.0. Bioinformatic prediction identified TCF7L2 as a common target gene of these lncRNAs, which is involved in the Wnt, Hippo, and MAPK signaling pathways. We also identified several miRNAs interacting with ADAMTS9-AS2. In a cohort of 50 tumor samples, we confirmed inverse associations between ADAMTS9-AS2 expression and levels of miR-106a-5p (rs = –0.46, p = 0.03) and miR-17-5p (rs = –0.41, p = 0.04). Collectively, these findings reveal novel co-regulated lncRNA–miRNA axes and suggest their involvement in key signaling networks in breast cancer, providing a foundation for future functional studies and potential therapeutic targeting.

Objectives. Lung cancer, representing a difficult-to-diagnose heterogeneous malignant neoplasm, is characterized by an asymptomatic course up to late stages, a high incidence of adverse outcomes, and a high probability of metastasis. Its most common form is non-small cell lung cancer (NSCLC). Recent studies have demonstrated a significant role of non-coding RNAs—in particular, microRNAs—in the development of NSCLC. MicroRNAs, which function as post-transcriptional regulators of the expression of protein-coding genes, including those associated with oncogenesis, are involved in the processes of cell proliferation, differentiation, and apoptosis. One of the approaches for regulating the expression of microRNAs themselves is to change the methylation of the CpG island adjacent to the microRNA gene or overlapping it. It has been shown that microRNA genes are several times more likely to undergo methylation than protein-coding genes. The aim of the present work is to study changes in the level of methylation of a number of microRNA genes and compile a potential panel of markers for the diagnosis and prognosis of NSCLC.Methods. Samples of NSCLC tumors were collected and clinically characterized at the Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation, Moscow, Russia. High-molecular-weight DNA was isolated from tissues using a standard method. The level of methylation was analyzed using bisulfite conversion of DNA and quantitative methyl-specific polymerase chain reaction with real-time detection. The significance of differences between the studied groups was assessed by the nonparametric Mann–Whitney U test for independent samples. Differences were considered significant at p < 0.05.Results. The analysis of methylation levels of microRNA genes revealed a significant (p < 0.05) increase in the methylation level of eight microRNA genes: MIR124-1/2/3, MIR125В-1, MIR129-2, MIR137, MIR375, MIR1258, and MIR339 (p < 0.01, false discovery rate ≤ 0.25). On the basis of receiver operating characteristic analysis, a panel of markers is proposed for the diagnosis of NSCLC according to the nature of methylation of the studied microRNA genes in the tumor and in the normal tissue.Conclusions. Our results, which contribute to the understanding of molecular mechanisms involved in NSCLC development, can be used in the development of new diagnostic and prognostic approaches in clinical oncology.

Background: Ovarian tumors are characterized by asymptomatic progression until their late stages, when at the time of diagnosis the patient already has extensive metastatic disease. In addition to lymphogenous and hematogenous metastasis in ovarian cancer, there are peritoneal dissemination and metastasis to the greater omentum with ascites; moreover, peritoneal carcinomatosis is the predominant route of metastasizing of ovarian cancer. Epigenetic factors, such as gene methylation, regulatory microRNAs and long non-coding RNAs (lncRNAs), contribute to progression of this cancer. Our previous bioinformatic and experimental studies have identified 13 genes of lncRNAs (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) hypermethylated in the ovarian neoplasms. Aim: To evaluate the clinical significance of methylation levels of 13 lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1) associated with various types of ovarian cancer metastasis, including lymphogenous, peritoneal, omental, and distant metastases. Methods: The methylation levels of lncRNA genes GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, PLUT/PDX1-AS1, SNHG1, SNHG6, SNHG12, SNHG17, TINCR, TP53TG1, TUG1 were analyzed by quantitative real-time methylation-specific polymerase chain reaction. We tested 122 duplicate samples of ovarian neoplasms, including 104 malignancies and 18 borderline tumors, as well as 45 peritoneal macro metastases, collected in the N.N. Blokhin National Medical Research Center of Oncology in 2020 to 2023. The study included 21 samples of primary tumor from patients with lymphogenous metastases, 45 samples from patients with peritoneal dissemination, 61 from those with omental metastases, 49 from patients with ascites, and 9 with distant metastases. Results: The tumor samples from the patients with lymphatic nodes metastases showed a significant increase in the methylation level of two lncRNA genes: SNHG6 (p = 0.044) and SNHG12 (p = 0.006). Peritoneal dissemination was associated with hypermethylation of four lncRNA genes: GAS5, HOTAIR, LINC00472 (p 0.05), and most significantly TINCR (p = 0.001). GAS5, HOTAIR, LINC00886 (p 0.05) and most significantly LINC00472 (p 0.001) hypermethylation was typical for omental metastasis, and that of LINC00472 and LINC00886, with ascites (p 0.05). Peritoneal macroscopic metastases demonstrated increased methylation of MAFG-DT (p 0.001) and TP53TG1 (p 0.001) and desmethylation of LINC00886 (p = 0.003) and SNHG12 (p = 0.002), compared to their primary tumors. Conclusion: We performed the analysis of clinical significance of 13 hypermethylated lncRNA genes in ovarian cancer and were the first to show that 10 genes (GAS5, HOTAIR, LINC00472, LINC00886, MAFG-DT, SNHG6, SNHG12, TINCR, TP53TG1, TUG1) were associated with various types of ovarian tumor metastasis. Also, we were able to determine certain panels of lncRNA, which, if demonstrate abnormal methylation, were specific for lymphogenous and peritoneal metastasis of ovarian tumors.

Metastasis to the lymph nodes is one of the most important factors in the poor prognosis of patients with breast cancer; the five-year survival rate for metastatic breast cancer is less than 30

There are three types of metastases in ovarian cancer: lymphogenous, hematogenous, and peritoneal. Dissemination of the tumor in the peritoneum is directly related with the development of ascites and a poor prognosis. The purpose of this study is to determine changes in the methylation level of a group of long non-coding RNA (lncRNA) genes at different stages of ovarian cancer progression. The methylation level of 7 lncRNA genes (LINC00472, LINC00886, MAFG-DT, SNHG1, SNHG6, TP53TG1, and TUG1) was studied by quantitative methyl-specific PCR in 93 samples of ovarian tumors and 75 paired samples of histologically normal tissue, as well as in 29 peritoneal macroscopic metastases. Using the nonparametric Mann—Whitney test, a significant (p<0.001) increase in the level of methylation of the LINC00886, SNHG1, SNHG6, and TUG1 genes in the tumor tissue was shown. For the LINC00472, LINC00886, and SNHG6 genes, a significant relationship was found with the clinical stage (p≤0.001), as well as with the appearance of metastases for the LINC00472 (p<0.001) and SNHG6 (p=0.005) genes. There was a significant increase in the level of methylation of MAFG-DT and TP53TG1 (p<0.001) genes, as well as a decrease in LINC00886 (p=0.003) in peritoneal metastases relative to the primary focus. Methylation of the LINC00472 and SNHG6 genes can be considered as a factor in initiating ovarian cancer metastasis, and methylation of the LINC00886, MAFG-DT, and TP53TG1 genes as a colonization factor for metastases in the peritoneum. Thus, a relationship between methylation of a group of lncRNA genes at different stages of ovarian cancer dissemination was shown, which is important for understanding the mechanisms of these processes and for developing innovative approaches to ovarian cancer therapy.

We analyzed changes in the level of methylation of CpG islands in four long non-coding RNA (lncRNA) genes MEG3, ZNF667-AS1, GAS5, and SEMA3B-AS1 as promising markers of breast cancer. Methylation analysis was performed by quantitative methylation-specific PCR on a set of 38 paired (tumor/normal) breast cancer samples. Significantly (p<0.001) increased methylation was shown for three of the four lncRNA genes: MEG3, ZNF667-AS1, and SEMA3B-AS1. We found significant correlations of the methylation level of all the studied lncRNA genes with the stage of cancer and with lymphogenic metastasis, and for MEG3 and ZNF667-AS1 also with the tumor size. Methylation of ZNF667-AS1, and SEMA3B-AS1 genes in breast cancer was detected for the first time. Based on these findings, new potential markers for the diagnosis and prognosis of breast cancer can be proposed.

Recently, more and more data have been accumulating indicating the role of long noncoding RNAs (lncRNAs) in the regulation of biological processes in cells, as well as in the mechanisms of cancer development and progression. Aberrant methylation of promoter regions of both protein genes and lncRNA genes can disrupt their expression and functional activity. Using bioinformatics databases, six lncRNA genes (GAS5, HOTAIR, LINC00472, LINC00886, SNHG17, and TUG1) with CpG islands differentially expressed and presumably hypermethylated in tumors of patients with ovarian cancer (OC) were selected. Using a sample of 93 OC samples, real-time methylation specific PCR showed a statistically significant (p < 0.05) increase in the level of methylation in tumors. Moreover, for the genes LINC00472, LINC00886, SNHG17, and TUG1, hypermethylation in OC was detected for the first time. Five genes (except SNHG17) showed a further increase in methylation levels at a more advanced stage, and four genes (except SNHG17 and LINC00886) showed a significant association with metastasis. Using real-time RT-PCR, differential changes in the expression level of the GAS5, HOTAIR, SNHG17, and TUG1 genes and a significant correlation of methylation with expression for the GAS5 gene were shown. Thus, hypermethylation associated with the progression and/or development of OC was detected for six lncRNA genes, which is important for elucidating the epigenetic processes involved in the pathogenesis of OC and can be used as new biomarkers of OC.

Our work aimed to evaluate and differentiate the role of ten lncRNA genes (GAS5, HAND2-AS1, KCNK15-AS1, MAGI2-AS3, MEG3, SEMA3B-AS1, SNHG6, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in the development and progression of epithelial ovarian cancer (EOC). A representative set of clinical samples was used: 140 primary tumors from patients without and with metastases and 59 peritoneal metastases. Using MS-qPCR, we demonstrated an increase in methylation levels of all ten lncRNA genes in tumors compared to normal tissues (p < 0.001). Using RT-qPCR, we showed downregulation and an inverse relationship between methylation and expression levels for ten lncRNAs (rs < -0.5). We further identified lncRNA genes that were specifically hypermethylated in tumors from patients with metastases to lymph nodes (HAND2-AS1), peritoneum (KCNK15-AS1, MEG3, and SEMA3B-AS1), and greater omentum (MEG3, SEMA3B-AS1, and ZNF667-AS1). The same four lncRNA genes involved in peritoneal spread were associated with clinical stage and tumor extent (p < 0.001). Interestingly, we found a reversion from increase to decrease in the hypermethylation level of five metastasis-related lncRNA genes (MEG3, SEMA3B-AS1, SSTR5-AS1, ZEB1-AS1, and ZNF667-AS1) in 59 peritoneal metastases. This reversion may be associated with partial epithelial-mesenchymal transition (EMT) in metastatic cells, as indicated by a decrease in the level of the EMT marker, CDH1 mRNA (p < 0.01). Furthermore, novel mRNA targets and regulated miRNAs were predicted for a number of the studied lncRNAs using the NCBI GEO datasets and analyzed by RT-qPCR and transfection of SKOV3 and OVCAR3 cells. In addition, hypermethylation of SEMA3B-AS1, SSTR5-AS1, and ZNF667-AS1 genes was proposed as a marker for overall survival in patients with EOC.

According to the latest global statistics for 2020, breast cancer (BC) has taken first place in the incidence of epithelial tumors, ahead of lung cancer, and is the main cause of mortality from cancer pathology among women around the world [...]

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.

Актуальность. Рак яичников (РЯ) представляет собой группу агрессивных гетерогенных злокачественных опухолей, характеризующихся быстрой прогрессией, низким диагностическим потенциалом, высокой частотой неблагоприятных исходов и высоким потенциалом метастазирования. В последнее время все большую актуальность приобретают исследования длинных некодирующих РНК (днРНК, lncRNAs), которые не обладают способностью кодировать белки. Для днРНК характерна высокая тканеспецифичность экспрессии, они участвуют в регуляции различных сигнальных путей в клетках, демонстрируя большой прогностический потенциал при онкозаболеваниях. Цель исследования – выявление аберрантно экспрессируемых длинных некодирующих РНК в образцах опухолей больных РЯ и связи уровней экспрессии с патофизиологическими характеристиками опухолей. Методика. Образцы опухолей РЯ собраны и клинически охарактеризованы в ФГБУ «НМИЦ онкологии им. Н.Н. Блохина». Высокомолекулярную РНК выделяли из ткани стандартным методом. Анализ уровня экспрессии днРНК HOTAIR, MALAT1 и TINCR проводился с использованием ПЦР в реальном времени готовой реакционной смесью qPCRmix-HS SYBR («Евроген»). Статистический анализ уровней экспрессии выполнен в программной среде R с применением непараметрического U теста Манна–Уитни. Корреляционный анализ выполняли с использованием метода ранговой корреляции Спирмена и рассчитывали уровень его значимости. Различия считали статистически значимыми при р < 0.05. Дополнительно были проанализированы данные по экспрессии днРНК при РЯ по базе данных GEPIA (http://gepia.cancer-pku.cn/). Результаты. Анализ уровня экспрессии днРНК показал значимое (p≤0.05) снижение уровня экспрессии днРНК HOTAIR, MALAT1. При анализе образцов с учётом патофизиологических характеристик опухоли было показано, что снижение уровня экспрессии HOTAIR ассоциировано с III/IV стадией опухолевого процесса. Для днРНК MALAT1 и TINCR показана значимая корреляция низкого уровня экспрессии с развитием эндометриоидного подтипа РЯ. Заключение. Представленные данные способствуют более глубокому пониманию механизмов развития РЯ и могут быть использованы при диагностике, прогнозе и выборе тактики лечения данной патологии. Background.Ovarian cancer (OC) is a group of aggressive heterogeneous malignant tumors characterized by rapid progression, low diagnostic potential, high incidence of adverse outcomes, and high potential for metastasis. Recently, studies of long non-coding RNAs (lncRNAs), which, with rare exceptions, do not have the ability to encode proteins, have become increasingly important. LncRNAs are characterized by high tissue-specific expression and they are involved in the regulation of various signaling pathways in cells and demonstrate a great prognostic potential in cancer. Aim. Detection of aberrantly expressed long non-coding RNAs in tumor samples from OC patients and association of expression levels with pathophysiological characteristics of tumors. Methods. Samples of OC tumors were collected and clinically characterized at the N.N. Blokhin Research Institute of Clinical Oncology. High molecular weight RNA was isolated from tissue by a standard method. Analysis of the expression levels of HOTAIR, MALAT1, and TINCR lncRNA was carried out using real-time PCR and a qPCRmix-HS SYBR ready-made reaction mixture (Evrogen). Statistical analysis of expression levels was performed in the R software environment using the nonparametric Mann-Whitney U test. Correlation analysis was performed using Spearman’s rank correlation, and its significance level was calculated. Differences were considered significant at p<0.05. Additionally, expression levels of these lncRNAs in OC were analyzed using the GEPIA database (http://gepia.cancer-pku.cn/). Results. The expression levels of the HOTAIR and MALAT1 lncRNA genes were significantly decreased (p≤0.05). Analysis of the samples with the account of the tumor pathophysiological characteristics showed that the decrease in the level of HOTAIR expression was associated with stage III/IV of the tumor process. For MALAT1 and TINCR lncRNAs, low expression levels significantly correlated with the development of the endometrioid subtype of OC. Conclusion. The results of the study allow a better insight into the mechanisms of OC development and can be used for diagnosis, prognosis and selection of therapeutic tactics in this pathology.

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive histological type of cancer in this location. Distant metastases are present in approximately 30% of patients at the time of first examination. Therefore, the ability to predict the occurrence of metastases in patients at early stages of the disease is an urgent task aimed at personalized treatment. Samples of tumor and paired histologically normal kidney tissue from patients with metastatic and non-metastatic ccRCC were studied. Gene expression was analyzed using real-time PCR. The level of gene methylation was evaluated using bisulfite conversion followed by quantitative methylation-specific PCR. Two groups of genes were analyzed in this study. The first group includes genes whose expression is significantly reduced during metastasis: CA9, NDUFA4L2, EGLN3, and BHLHE41 (p < 0.001, ROC analysis). The second group includes microRNA genes: MIR125B-1, MIR137, MIR375, MIR193A, and MIR34B/C, whose increased methylation levels are associated with the development of distant metastases (p = 0.002 to <0.001, ROC analysis). Based on the data obtained, a combined panel of genes was formed to identify patients whose tumors have a high metastatic potential. The panel can estimate the probability of metastasis with an accuracy of up to 92%.

Актуальность. Одним из самых распространенных злокачественных новообразований является рак легкого. Его самой распространенной формой, более 85% всех случаев, является немелкоклеточный рак легкого (НМРЛ). Одним из генов, тесно связанным с возникновением и прогрессией этого вида рака, является ген DAPK1, эпигенетическая регуляция которого, происходит на разных уровнях, в частности, метилирование промоторного CpG-островка гена или же влияние изменения уровня экспрессии микроРНК, для которых ген DAPK1 является геном-мишенью. Вопрос о влиянии метилирования и/или микроРНК на регуляцию экспрессии мРНК гена DAPK1 при НМРЛ остается открытым. Цель. Исследование изменений уровня экспрессии и/или метилирования микроРНК и их гена-мишени DAPK1 при НМРЛ. Методика. Образцы опухолей НМРЛ собраны и клинически охарактеризованы в НИИ клинической онкологии ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России. Высокомолекулярную ДНК выделяли из ткани стандартным методом. Анализ уровня метилирования проводили с применением бисульфитной конверсии ДНК и количественной метилспецифичной ПЦР (МС-ПЦР) с детекцией в реальном времени. Методом ОТ-ПЦР в реальном времени определены уровни экспрессии 4 микроРНК и их предполагаемого гена-мишени DAPK1. Статистический анализ выполнен с использованием программного пакета IBM SPSS 22. Различия считали достоверными при р<0.05. Результаты. С применением метилспецифичной ПЦР в реальном времени показано статистически значимое (р<0.05) увеличение уровня метилирования гена DAPK1 в образцах опухолей по сравнению с парной гистологически нормальной тканью легкого. Показано, что уровень экспрессии мРНК гена DAPK1 статистически значимо ассоциирован как с изменением уровня метилирования промоторного CpG-островка гена DAPK1 (Rs=-0.517, p=0.002), так и с изменением уровня экспрессии исследованных микроРНК. В результате анализа уровней экспрессии DAPK1 и микроРНК были составлены две пары miR-339-3p – DAPK1 (Rs= -0.476, p=0.004) и miR-375 – DAPK1 (Rs= -0.354, p=0.037), позволяющие говорить о существенном влиянии этих микроРНК на регуляцию активности гена DAPK1. Заключение. Обнаруженные нами новые закономерности представляют интерес для понимания механизмов развития НМРЛ и могут лечь в основу диагностики и прогноза течения этой болезни, а также помочь скорректировать ход лечения с учетом патофизиологических особенностей опухоли. Background. Lung cancer is one of the most common malignant neoplasms. Non-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer, that accounts for more than 85% for all cases. The DAPK1 gene is one of the genes closely associated with the emergence and progression of this cancer. Epigenetic regulation of the DAPK1 gene occurs at different levels, in particular, by CpG island gene promoter methylation or by changes in the expression level of microRNAs, for which the DAPK1 gene is a target gene. The question of the effect of methylation and/or microRNAs on the regulation of the DAPK1 gene mRNA expression in NSCLC remains open. Aim. Detection of changes in the level of expression and/or methylation of microRNAs and their target gene DAPK1 in NSCLC. Methods. Samples of NSCLC tumors were collected and clinically characterized at the Research Institute of Clinical Oncology of the Blokhin National Research Center of Oncology. High-molecular DNA was isolated from the tissue by a standard method. The methylation level was determined using bisulfite DNA conversion and quantitative methyl-specific PCR (MS-PCR) with real-time detection. The levels of expression of 4 microRNAs and their putative target gene DAPK1 were determined by real-time PCR (RT-PCR). Statistical analysis was performed using an IBM SPSS 22 software package. The differences were considered significant at p<0.05. Results. The analysis with MS RT-PCR showed a statistically significant (p<0.05) increase in the level of methylation of the DAPK1 gene in tumor samples in comparison with paired histologically normal lung tissue. The level of the DAPK1 gene mRNA expression was statistically significantly associated with both the change in the methylation level of the DAPK1 gene promoter CpG island (Rs=-0.517, p=0.002) and the change in the expression of studied microRNA. The analysis of expression levels of DAPK1 and microRNAs allowed creation of two pairs, miR-339-3p – DAPK1 (Rs= -0.476, p=0.004) and miR-375 – DAPK1 (Rs= -0.354, p=0.037), which suggested a significant effect of these microRNAs on the regulation of DAPK1 gene activity. Conclusion. Thus, the newly discovered patterns are of interest for understanding the mechanisms of NSCLC development. They can form a basis for diagnosis and prognosis of this disease and also help adjustment of the treatment taking into account pathophysiological features of the tumor.

Long non-coding RNAs (lncRNAs) are crucial players in the pathogenesis of non-small-cell lung cancer (NSCLC). A competing binding of lncRNAs and mRNAs with microRNAs (miRNAs) is one of the most common mechanisms of gene regulation by lncRNAs in NSCLC, which has been extensively researched in the last two decades. However, alternative mechanisms that do not depend on miRNAs have also been reported. Among them, the most intriguing mechanism is mediated by RNA-binding proteins (RBPs) such as IGF2BP1/2/3, YTHDF1, HuR, and FBL, which increase the stability of target mRNAs. IGF2BP2 and YTHDF1 may also be involved in m6A modification of lncRNAs or target mRNAs. Some lncRNAs, such as DLGAP1-AS2, MALAT1, MNX1-AS1, and SNHG12, are involved in several mechanisms depending on the target: lncRNA/miRNA/mRNA interactome and through RBP. The target protein sets selected here were then analyzed using the DAVID database to identify the pathways overrepresented by KEGG, Wikipathways, and the Reactome pathway. Using the STRING website, we assessed interactions between the target proteins and built networks. Our analysis revealed that the JAK-STAT and Hippo signaling pathways, cytokine pathways, the VEGFA-VEGFR2 pathway, mechanisms of cell cycle regulation, and neovascularization are the most relevant to the effect of lncRNA on NSCLC.

Breast cancer (BC) remains one of the leading causes of cancer deaths among women worldwide. Recently, studies of long non-coding RNAs (lncRNAs) involved in the regulation of various signaling pathways in cells have become increasingly important, since they demonstrate great prognostic potential in cancer. The aim of our work was to identify new aberrantly expressed lncRNAs in BC. We identified 30 aberrantly expressed lncRNAs in BC. For most lncRNAs, a decrease in the expression level by 2.34–13.2 times (p < 0.05) was noted, and only for lncRNA TERC, an increase in the expression level by 2.24 times (p = 0.034) was noted. Of greatest interest are the data obtained for the lncRNAs ADAMTS9-AS2, EMX2OS, HOTAIRM1 and MEG3, as they are consistent with the data of the bioinformatic analysis.

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.

We studied changes in the level of methylation of a number of microRNA genes hypermethylated in non-small cell lung cancer and its histological subtypes as well as the relationship of methylation of a group of microRNA genes with clinical and morphological features of the tumor with smoking status. A significantly high level of methylation of 7 genes (MIR124-1/3, MIR125B-1, MIR129-2, MIR137, MIR1258, and MIR339) was revealed in adenocarcinoma and squamous cell lung cancer in comparison with samples of adjacent histologically unchanged lung tissue. In squamous cell lung cancer, a significantly high level of methylation of the MIR124-2 gene in the tumor was also shown. In addition, differences in the methylation profile of adenocarcinoma and squamous cell carcinoma at stages III-IV of the oncological process were revealed. A high level of methylation of the MIR137 and MIR1258 genes was shown for adenocarcinoma and MIR339, MIR129-2, and MIR124-2 for squamous cell carcinoma. Significant differences in the level of methylation of MIR124-2 and MIR375 genes were revealed for smoking patients with squamous cell lung cancer.

БИОИНФОРМАТИЧЕСКИЙ СКРИНИНГ НЕКОДИРУЮЩИХ РНК, ВОВЛЕЧЕННЫХ В ПАТОГЕНЕЗ ЭПИТЕЛИАЛЬНОГО РАКА ЯИЧНИКОВЛ.А.Урошлев., И.В.Пронина, А.М Бурденный, В.И.Логинов, Э

The role of methylation of 9 miRNA genes in the pathogenesis of metastatic clear cell renal cell carcinoma was determined by quantitative methylation-specific PCR (MS-PCR). For 5 genes (MIR125B-1, MIR137, MIR193A, MIR34B/C, and MIR375), a significant correlation of high methylation level with late (III-IV) stages, large size (T3+T4) of the tumor, and metastasis to lymph nodes and/or distant organs was revealed. For another group of genes (MIR125B-1, MIR1258, MIR193A, MIR34B/C, and MIR375), a statistically significant correlation of high methylation level with loss of differentiation in the tumor (G3-G4) was found, and the opposite pattern was found for MIR203A. A total of 7 microRNA genes (MIR125B-1, MIR1258, MIR137, MIR193A, MIR203A, MIR34B/C, and MIR375) were identified, the methylation of which is associated with the progression of metastatic clear cell renal cell carcinoma. For 6 of them (except MIR34B/C) these data were obtained for the first time. Thus, new factors of the development and progression of clear cell renal cell carcinoma were identified as potential biomarkers for the early diagnosis and prognosis of metastatic clear cell renal cell carcinoma.