POLYMORPHISMS INVOLVED WITH MIRNA SYNTHESIS: ASSOCIATION WITH ENDOMETRIOSIS AND CANCER

Vol 1, 2020 - 131294
Iniciação Científica
Favorite this paper
How to cite this paper?
Abstract

INTRODUCTION AND OBJECTIVES: Endometriosis is a multifactorial gynecological disease and some advanced cases of endometriosis have an increased risk of developing epithelial ovarian cancer. Although, etiology of endometriosis is not entirely understood, it is recognized that genetic factors may contribute to development of the disease. microRNAs are a class of small non-coding RNAs that regulate post-transcriptional gene expression, influencing on various eukaryotic processes such as proliferation, differentiation, cell migration, oncogenesis. Some studies have shown that many conditions have been associated with down or up-regulation in the expression of certain microRNAs. This difference in gene expression may be explained by the occurrence of single nucleotide polymorphisms (SNPs) in microRNAs coding genes. DROSHA and DICER1 enzymes participate of the main stages of the microRNAs synthesis. Polymorphisms (rs10719 and rs3742330) can influence the stability and genes expression, and affect the binding of miRNAs. Therefore, the objective of the present study was to evaluate the association of DROSHA and DICER1 SNPs in the development of endometriosis and different conditions. MATERIAL AND METHODS: First, a case-control study was performed with 240 endometriosis cases and 242 controls. This study was approved by the Human Research Ethics Committees of HFSE (Protocol: 414/2011) and HMF (Protocol: 1.244.294/2015). DROSHA rs10719 G>A and DICER1 rs3742330 A>G SNPs were genotyped by TaqMan system and a binary logistic regression was used to evaluate the association between SNPs and endometriosis. Moreover, a literature review was performed using all published article (Pubmed database) regarding the association of the studied SNPs and different conditions, included cancer. RESULTS AND CONCLUSION: DROSHA rs10719AA was observed in 20.2% of controls, 21,9% of women with endometriosis and 21.4% of deep infiltrative endometriosis (DIE), while DICER1 rs3742330GG was only found in the women with endometriosis (2.1%) and DIE (2.5%). The frequency of the DICER1 rs3742330GG was significantly different between endometriosis cases and controls (P < 0.05), suggesting a tendency to present increased risk for endometriosis and DIE. It was observed differences in the allele’s frequencies of DROSHA rs10719A (6 - 79%) and DICER1 rs3742330G (10.2 - 55.1%) among populations. Both SNPs were risk factors for colorectal and bladder cancer. Also, DICER1 rs3742330 SNP was protective factor to precancerous cervical lesion, papillary thyroid carcinoma, hepatocellular carcinoma, gastric and prostate cancer. The results suggest that only DICER1 rs3742330 A>G SNP may be associated with susceptibility to endometriosis. Also, the frequency of both SNPs was significantly different among populations. Therefore, the study of this variant involved in gene expression regulation is important to help understand the etiopathogenesis of endometriosis and cancer.

Questions (2 topics)

Share your ideas or questions with the authors!

Did you know that the greatest stimulus in scientific and cultural development is curiosity? Leave your questions or suggestions to the author!

Sign in to interact

Have a question or suggestion? Share your feedback with the authors!

Author

Matheus Pereira de Mello

  1. Sim, esses SNPs ocorrem nos genes que codificam essas duas proteínas. Eles estão localizados na região 3’ UTR. Como esses SNPs estão presentes na região 3’ UTR, eles podem afetam a estabilidade de RNAm, e com isso interferem nos resíduos de adenina da cauda poliA, podendo diminuir a produção de proteína. Com base na literatura científica, o caso da presença de DICER1 rs3742330 G, há uma diminuição da expressão, o que acarreta a redução da clivagem de RNA, repressão da tradução e aumento da migração celular e angiogênese, levando assim a influência do desenvolvimento da endometriose. No DROSHA rs10719 A SNP é descrito um aumento na expressão de miRNA, entretanto não foi feito uma associação significativa à endometriose.
 
  1. O programa utilizado foi o SPSS. Foi considerado todas as variantes possíveis, pois o objetivo era avaliar possíveis fatores genéticos e ambientais associados.
 
  1. Levando em conta a literatura e nossos estudos, o SNP DICER1 rs3742330 G pode ser considerado um possível fator de risco para a endometriose. Todavia, pode ter alguns vieses, como a quantidade de pacientes (N) ser pequeno e sua frequência na população é baixa. Além disso, foi encontrado somente o alelo variante na população de casos e nenhum em controles, o que pode ser encontrada uma relevância clínica para um possível marcador genético.
Author

Matheus Pereira de Mello

1.    Em relação aos procedimentos, eu não fiz todos. Participei de extrações de DNA, pesquisa e revisão da bibliografia e montagem de tabelas. As análises estatísticas e epidemiológicas foram feitas pela minha orientadora.  2.    Sim, não foi um estudo prospectivo. Nós fizemos uma revisão sistemática. 3.    O próximo passo desse estudo seria a publicação em um periódico de relevância na comunidade científica.
Institutions
  • 1 Centro Universitário Estadual da Zona Oeste
  • 2 Grupo de Oncologia Molecular / Instituto Português de Oncologia / Instituto Português de Oncologia
  • 3 National Institute of Traumatology and Orthopaedics
Keywords
Endometriosis
Câncer
Polymorphisms
MicroRNA