scholarly journals Role of methylation of MIR-129-2, MIR-9-1, MIR-9-3, MIR-130b, MIR-107, and MIR-1258 miRNA genes in the pathogenesis and progression of breast cancer

2018 ◽  
pp. 115-118
Author(s):  
Е.А. Филиппова ◽  
А.М. Бурдённый ◽  
С.С. Лукина ◽  
И.В. Пронина ◽  
Т.П. Казубская ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Regional Lymph Nodes ◽  
Protein Coding ◽  
Specific Pcr ◽  
Mirna Genes ◽  
Progression Of Disease ◽  
Microrna Genes ◽  
Selection Of

Согласно последним эпигеномным исследованиям, доля гиперметилируемых генов микроРНК в несколько раз выше доли белок-кодирующих генов, что делает их перспективными маркерами опухолей. Цель исследования - обнаружение новых генов микроРНК, изменяющих уровень метилирования при раке молочной железы, и изучение их связь с развитием заболевания. Для 5 из 6 исследованных генов микроРНК: MIR-1258, -130b, -9-1, -9-3, -129-2 - методом метилспецифичной ПЦР отмечено статистически значимое (p < 0,01) повышение частот метилирования в 70 образцах опухолей молочной железы в сравнении с гистологически неизмененной тканью той же пациентки. Установлены значимые (p < 0,05) ассоциации частот метилирования 3 генов с такими параметрами прогрессии рака, как более тяжелая стадия (III-IV) рака (MIR-9-3 и MIR-1258), низкий уровень дифференцировки (MIR-107 и MIR-1258), размер опухоли (MIR-9-3), метастазы в регионарных лимфатических узлах и отдаленные метастазы (MIR-1258). Выявленные особенности метилирования исследованных генов могут найти клиническое применение для разработки современных подходов к профилактике, прогнозированию и выбору тактики лечения РМЖ. Epigenome studies have shown that the proportion of hypermethylated microRNA genes is several times higher than of protein-coding genes, which makes them promising markers of tumors. The aim of this study was to expand the spectrum of the miRNA genes hypermethylated in breast cancer and to investigate their connection with progression of disease. The methylation-specific PCR performed on a set of 70 breast cancer samples showed a significant increase in methylation frequency in tumor samples compared with histologically unchanged breast tissue for 5 of 6 studied microRNA genes - MIR-1258, -130b, -9-1, -9-3, and -129-2 (p < 0.01). Statistically significant (p < 0.05) associations of hypermethylation of 3 genes with parameters of cancer progression were established: for the MIR-9-3 and MIR-1258 genes - with more severe stages (III-IV) of cancer; MIR-107 and MIR-1258 - with a low level of tumor differentiation; MIR-9-3 - with tumor size; MIR-1258 - with metastases to regional lymph nodes or distant organs. The identified methylation features of the studied genes can find clinical application in development of modern approaches to prediction, prevention, and selection of tactics for the treatment of breast cancer.

The Role of microRNA Genes in Breast Cancer Progression and Metastasis.

2009 ◽  
Author(s):  
C. Johnstone ◽  
E. Lucas ◽  
L. Kusdra ◽  
A. Goga ◽  
R. Anderson
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Breast Cancer Progression ◽  
Microrna Genes

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

scholarly journals Regulation of Breast Cancer and Bone Metastasis by MicroRNAs

2013 ◽  
Vol 35 ◽  
pp. 369-387 ◽  
Author(s):  
S. Vimalraj ◽  
P. J. Miranda ◽  
B. Ramyakrishna ◽  
N. Selvamurugan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Bone Metastasis ◽  
Cancer Progression ◽  
Human Breast ◽  
Protein Coding ◽  
Regulate Gene Expression ◽  
Complex Process ◽  
And Function

Breast cancer progression including bone metastasis is a complex process involving numerous changes in gene expression and function. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that regulate gene expression by targeting protein-coding mRNAs posttranscriptionally, often affecting a number of gene targets simultaneously. Alteration in expression of miRNAs is common in human breast cancer, possessing with either oncogenic or tumor suppressive activity. The expression and the functional role of several miRNAs (miR-206, miR-31, miR-27a/b, miR-21, miR-92a, miR-205, miR-125a/b, miR-10b, miR-155, miR-146a/b, miR-335, miR-204, miR-211, miR-7, miR-22, miR-126, and miR-17) in breast cancer has been identified. In this review we summarize the experimentally validated targets of up- and downregulated miRNAs and their regulation in breast cancer and bone metastasis for diagnostic and therapeutic purposes.

Hypermethylation of a group of microRNA genes in primary tumors and peritoneal metastases of ovarian cancer

2018 ◽  
pp. 58-66
Author(s):  
А.М. Бурдённый ◽  
Д.О. Уткин ◽  
Е.А. Филиппова ◽  
В.И. Логинов ◽  
И.В. Пронина ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Progression ◽  
Ovarian Tissue ◽  
Methylation Status ◽  
Peritoneal Metastases ◽  
Primary Tumors ◽  
Specific Pcr ◽  
Mirna Genes ◽  
Metastatic Activity ◽  
Microrna Genes

Рак яичников отличает раннее метастазирование и высокая частота летальных исходов. Ранее нами определена группа генов микроРНК, метилирование которых вовлечено в развитие и прогрессию рака яичников. Цель исследования - расширить спектр генов микроРНК, гиперметилируемых при раке яичников, и изучить их связь с метастазированием как в образцах первичных опухолей, так и в макрометастазах. Методика . Использовали метод бисульфитной конверсии ДНК с последующей метилспецифичной ПЦР. Результаты . На выборке из 54 образцов рака яичников показано значимое повышение частот метилирования в образцах опухолей в сравнении с гистологически неизмененной тканью яичников для 6 из 7 исследованных генов микроРНК: MIR-107, MIR-1258, MIR-130b, MIR-34b/c, MIR-9-1, MIR-9-3 ( p <10, FDR = 0,01). Установлены статистически-значимые ассоциации метилирования 5 генов с параметрами прогрессии рака, в частности - с метастазированием. При сравнении данных по частотам метилирования в образцах опухолей от 37 пациенток без метастазов и 17 пациенток с метастазами, статистически значимая ассоциация с метастазированием показана для MIR-1258 ( p <0,04), MIR-130b ( p <0,01), MIR-34b/c ( p <0,001), и на уровне тенденции - для MIR-9-1, MIR-9-3 . При анализе первичных опухолей и перитонеальных метастазов от 13 пациенток для этих 5 генов подтверждена связь с метастазированием. Заключение . Выявлена системная роль гиперметилирования группы генов микроРНК в перитонеальном метастазировании у больных раком яичников. Ovarian cancer is characterized by the early metastatic activity and high frequency of poor prognosis. Earlier we described a group of miRNA genes where methylation is involved in the development and progression of ovarian cancer. Aim. To expand the array of miRNA genes hypermethylated in ovarian cancer and to study their correlation with metastatic activity both in primary tumors and macro-metastases. Methods. For our study, we used DNA bisulfite conversion followed by methyl-specific PCR. Results. A significant increase in methylation frequency was observed in 54 samples of ovarian cancer compared with histologically intact ovarian tissue for 6 of 7 studied miRNA genes, MIR-107, MIR-1258, MIR-130b, MIR-34b/c, MIR-9-1, and MIR-9-3 ( p <10, FDR = 0.01). Five miRNA genes statistically significantly correlated with cancer progression, particularly with the metastatic activity. When comparing the methylation status of tumor samples from 37 non-metastatic and 17 metastatic patients we found statistically significant correlations with metastasis for MIR-1258 ( p <0.04), MIR-130b ( p <0.01), and MIR-34b/c ( p <0.001), and tendencies for MIR-9-1 and MIR-9-3 . Analysis of primary tumors and matched peritoneal metastases in 13 patients confirmed the association between methylation and metastasis for these 5 genes. Conclusion. This study demonstrated a systemic role of hypermethylation for the group of miRNA genes in peritoneal metastasis in patients with ovarian cancer.

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