Long noncoding RNAs (lncRNAs) have been identified as contributors to the development and progression of cancer through various functions and mechanisms. LncRNA GAS5 is downregulated in multiple cancers and acts as a tumor suppressor in breast cancer. GAS5 interacts with various proteins (e.g., E2F1, EZH2, and YAP), DNA (e.g., the insulin receptor promoter), and various microRNAs (miRNAs). In breast cancer, GAS5 binds with miR-21, miR-222, miR-221-3p, miR-196a-5p, and miR-378a-5p that indicates the presence of several elements for miRNA binding (MREs) in GAS5. Mediated by the listed miRNAs, GAS5 is involved in the upregulation of a number of mRNAs of suppressor proteins such as PTEN, PDCD4, DKK2, FOXO1, and SUFU. Furthermore, the aberrant promoter methylation is involved in the regulation of GAS5 gene expression in triple-negative breast cancer and some other carcinomas. GAS5 can stimulate apoptosis in breast cancer via diverse pathways, including cell death receptors and mitochondrial signaling pathways. GAS5 is also a key player in the regulation of some crucial signal pathways in breast cancer, such as PI3K/AKT/mTOR, Wnt/β-catenin, and NF-κB signaling. Through epigenetic and other mechanisms, GAS5 can increase sensitivity to multiple drugs and improve prognosis. GAS5 is thus a promising target in the treatment of breast cancer patients.

Our work aimed to differentiate 20 aberrantly methylated miRNA genes that participate at different stages of development and metastasis of ovarian carcinoma (OvCa) using methylation-specific qPCR in a representative set of clinical samples: 102 primary tumors without and with metastases (to lymph nodes, peritoneum, or distant organs) and 30 peritoneal macroscopic metastases (PMM). Thirteen miRNA genes (MIR107, MIR124-2, MIR124-3, MIR125B-1, MIR127, MIR129-2, MIR130B, MIR132, MIR193A, MIR339, MIR34B/C, MIR9-1, and MIR9-3) were hypermethylated already at the early stages of OvCa, while hypermethylation of MIR1258, MIR137, MIR203A, and MIR375 was pronounced in metastatic tumors, and MIR148A showed high methylation levels specifically in PMM. We confirmed the significant relationship between methylation and expression levels for 11 out of 12 miRNAs analyzed by qRT-PCR. Moreover, expression levels of six miRNAs were significantly decreased in metastatic tumors in comparison with nonmetastatic ones, and downregulation of miR-203a-3p was the most significant. We revealed an inverse relationship between expression levels of miR-203a-3p and those of ZEB1 and ZEB2 genes, which are EMT drivers. We also identified three miRNA genes (MIR148A, MIR9-1, and MIR193A) that likely regulate EMT–MET reversion in the colonization of PMM. According to the Kaplan–Meier analysis, hypermethylation of several examined miRNA genes was associated with poorer overall survival of OvCa patients, and high methylation levels of MIR130B and MIR9-1 were related to the greatest relative risk of death.

Human malignant tumors are characterized by extensive changes in DNA methylation patterns. These changes include global hypomethylation of the tumor cell genome and local hypermethylation of CpG islands, many of which are associated with gene promoters and regulation of their expression [5]. Moreover, hypomethylation of DNA contributes to genome instability, and hypermethylation of promoters serves to inactivate suppressor genes involved in suppressing the processes of malignant transformation and cancer progression. Hypo-and hypermethylation of the tumor genome are included in the set of the main features of cancer (hallmarks of cancer) [7]. Breast cancer (BC) is the most common type of cancer in women in both developed and developing countries, accounting for 1 / 10 of all malignant tumors [6]. Significant advances in diagnostic and therapeutic approaches have been made in recent decades, but BC is still the second most common cause of cancer death in women, which determines the need to search for new markers.Currently, the prospects of using microRNAs as markers for diagnosing BC, predicting its course, and evaluating the individual response of the body to ther-

No abstract

No abstract

No abstract

Changes in the methylation levels of 21 microRNA genes in 91 breast cancer samples in comparison with paired samples of histologically unchanged tissue were studied by quantitative methylation-specific PCR. For 19 microRNA genes, a significant increase in the methylation level in tumors in comparison with normal tissues was shown (Mann-Whitney test). When considering the data for breast cancer samples only from patients with clinical stages I and II (59samples), 17 genes with a significantly increased level of methylation were identified. Increased methylation level for 11 genes (MIR124-

Офтальмологическим проявлением болезни Шегрена (БШ) и ревматоидного артрита (РА) является сухой кератоконъюнктивит (СКК). Цель исследования-изучение взаимосвязи полиморфных маркеров rs7947461(C/T), rs915956 (C/T), rs4144331 (C/A) гена TRIM21со степенью тяжести СКК при РА и БШ. Материал и методы. Обследовано 70 пациентов с диагнозом РА (n=27) и БШ (n=43). Группа контроля-добровольцы без РА и БШ в анамнезе (n=35). Идентификацию аллелей полиморфного маркера С660Т rs7947461 гена TRIM21 выполняли методом ПЦР-ПДРФ; полиморфного маркера rs915956 (C/T) и rs4144331 (C/A) гена TRIM21-анализом кривых плавления ДНК. Результаты. Для предрасполагающего генотипа (TT) полиморфного маркера rs7947461 выявлена ассоциация с риском развития тяжелой степени СКК. Генотип АА полиморфного маркера rs4144331 был обнаружен только при тяжелой степени СКК (c 2 =7,74; OR=17,46, CI 95% =(1,96-318,38), p=0,02). Заключение. Установлена ассоциация rs7947461 (rs660) и rs4144331 с риском развития тяжелой степени СКК.