The Genetic Background of Endometriosis: Can ESR2 and CYP19A1 Genes Be a Potential Risk Factor for Its Development?
Abstract
:1. Introduction
2. The Genetic Background of Endometriosis
2.1. MicroRNA (MiRNA)
2.2. Long Noncoding RNA (lncRNA)
2.3. Genome-Wide Association Studies (GWAS)
3. The Role of the ESR2 and CYP19A1 Genes in Endometriosis
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- to stimulate the development of female genital organs;
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- to form secondary and tertiary sexual characteristics;
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- to stimulate proliferation of the stromal cells in endometrium and the growth of the uterine muscle mass, as well as the peristalsis of the uterus and of the ovarian ducts; and
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- to stimulate the development of the breasts and of the external genital organs, in preparation of the breasts for lactation [77].
4. The Expression of ESR2 and CYP19A1 Genes among Women with Endometriosis as a Potential Risk Factor for the Development of the Disease
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- The control of transcription of the p450 isoenzyme encoding genes,
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- The mRNA stabilization, and
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- Post-translative modifications.
5. Conclusive Summary
Author Contributions
Funding
Conflicts of Interest
References
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Biological Process in Cells | miRNA Type |
---|---|
Hypoxia | MiR-20a, miR-148a |
Survival and proliferation | miR-10b, miR-29c, miR-100, miR-143, miR-145, miR-183, miR-202, miR-210, miR-451 |
The inflammatory state | miR-302a, miR-542-3p |
Steroidogenesis | miR-142-3p, miR-23, miR-135 |
Reconstruction and angiogenesis | miR-21, miR-93, miR-199a-5p, miR-210, miR-520g |
IncRNA Type | |||||
---|---|---|---|---|---|
Expression Increase | Expression Decrease | ||||
Plasma a | Ectopic Endometrium in the Ovary b | Eutopic Endometrium c | Plasma a | Ectopic Endometrium in the Ovary b | Eutopic Endometrium c |
NAPA-AS1-202 RAB-203 | CHL-AS2 LOC255167 LOC400043 XLOC_012904 XLOC_12_009510 AFAP1-AS1 | AC068282.3 XLOC_004134 GBP1P1 RP11-369C8.1 AX746484 BC025370 | NIT2-203 PEF1-206 MTMR11-206 CCDC91-218 POLD4-204 | LOC100505776 UCA1 XLOC_012981 LINC00261 LOC100507043 LOC440335 | RP11-403H13.1 RP11-679C8.2 RP11-77A13.1 RP11-408H2.0.1 CHRM3-AS2 AC007246.3 |
Gene | Function |
---|---|
WNT4 | The gene encoding a protein which is necessary for the development of the female genital tract. In mice, deprived of the WNT4 gene, there is almost a complete lack of the Müllerian ducts and their derivatives [45]. WNT expression was shown in the peritoneum and endometrium [46]. |
GREB1 | The gene of early response on the pathway of oestrogen regulation, which is involved in the hormone-dependent growth of breast cancer cells. Its expression grows in endometriotic lesions of the peritoneum, in comparison with eutopic endometrium. It plays some role in the oestrogen-dependent development of endometriosis [47]. |
ETAA1 | It encodes the surface antigen, specific for the neoplasms of the Ewing’s sarcoma family (a group of neoplasms which are formed in the bone or in the soft tissue and develop from the same type of stem cells in the body [48]. |
FN1 | It is involved in the processes of adhesion and migration of cells, including embryogenesis, wound healing processes, blood coagulation, host protection and metastases [49]. It has been demonstrated that the SOX2 gene, which is a transcriptive factor for FN1, controls the migration of cells in ovarian cancer [50] |
ID4 | The ovarian oncogene which participates in control of the methylation pathway during breast cancer formation [51]. Its elevated expression occurs in the ovary and in the cell lines of endometrial cancer and breast cancer [52]. |
NFE2L3 | A transcriptive factor, the contribution of which is suggested in the process of differentiation of cells, the inflammatory state and carcinogenesis [53]. Its enhanced expression has been demonstrated in the human cells of breast cance [54] and in tissue samples of testis cancer [55]. |
miRNA_148a | This microRNA takes part in the signalling pathway of Wnt/β-catenin whoch may play some role in the development of endometriosis via homeostasis regulation by the sex hormone [56] and fibrogenesis [57]. |
HOX A10 | It belongs to the homeobox family of transcription factors, which plays an important role in the differentiation of the Müllerian duct to the ovarian duct, the uterus, the uterine cervix and the vagina [58]. |
CDKN2B-AS1 | It is involved in the regulation of the suppressor genes: CDKN2B, CDKN2A and ARF. CDKN2A inactivation has been described in endometriosis and endometrial cancer [59]. |
VEZT | It encodes a protein which is the main component of the cadherin-catenin complex, necessary to create and maintain the adherens junctions. This protein undergoes expression in the majority of epithelial cells and is of key importance for the formation of cell junctions. It is also an important suppressor gene, impacting the genes associated with migration and invasion of cells, the growth genes, the genes of adhesive cells and the TCF19 gene. TCF19 is a potential transactivating factor which may play an important role in the transcription of genes required for the later stages of cell cycle progression. TCF19 takes part in keeping the immunological balance [60]. |
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Smolarz, B.; Szyłło, K.; Romanowicz, H. The Genetic Background of Endometriosis: Can ESR2 and CYP19A1 Genes Be a Potential Risk Factor for Its Development? Int. J. Mol. Sci. 2020, 21, 8235. https://doi.org/10.3390/ijms21218235
Smolarz B, Szyłło K, Romanowicz H. The Genetic Background of Endometriosis: Can ESR2 and CYP19A1 Genes Be a Potential Risk Factor for Its Development? International Journal of Molecular Sciences. 2020; 21(21):8235. https://doi.org/10.3390/ijms21218235
Chicago/Turabian StyleSmolarz, Beata, Krzysztof Szyłło, and Hanna Romanowicz. 2020. "The Genetic Background of Endometriosis: Can ESR2 and CYP19A1 Genes Be a Potential Risk Factor for Its Development?" International Journal of Molecular Sciences 21, no. 21: 8235. https://doi.org/10.3390/ijms21218235