RESUMO
Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.
Assuntos
Aborto Habitual/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Apoptose/fisiologia , Proliferação de Células/fisiologia , MicroRNAs/metabolismo , Trofoblastos/metabolismo , Adulto , Linhagem Celular , Feminino , Humanos , Gravidez , Trofoblastos/citologia , Regulação para CimaRESUMO
OBJECTIVE: To investigate the relationship between -344T polymorphism in aldosterone synthetase (CYP11B2) gene promoter region and the pathogenesis of polycystic ovary syndrome (PCOS). METHODS: Ninety two patients with PCOS and controls were genotyped according to the fragment length (273 bp and or 202 bp) of CYP11B2 gene promoter by the technique of polymerase chain reaction-restriction fragment length polymorphism. The levels of luteinizing hormone, follicular stimulating hormone, estrodiol, progesterone, prolactin, testosterone, plasma renin activity (PRA), plasma angiotensin II (PANG II) and aldosterone in the basal state were also determined. Different genotypes between PCOS were compared about their levels of PRA, PANG II, aldosterone and testosterone. RESULTS: (1) The C allele frequencies of CYP11B2 gene in control and PCOS was 22% and 36%, respectively. (2) The frequency of variants (TC, CC) of CYP11B2 gene -344T polymorphism site in PCOS (57%) was significantly higher than that of control subjects (37%). (3) The level of PRA, PANG II, aldosterone, testosterone were all significantly higher in the genotype of -344CC than in that of -344TT in PCOS and normal women (P < 0.01). CONCLUSIONS: (1) The variants (T-->C) of -344T polymorphism site of CYP11B2 gene predisposes increased risk of PCOS. (2) The genotype of -344CC, -344TC may be susceptible genotype of PCOS and has related to the enhanced functional activity of ovarian renin angiotensin system in PCOS.