miR-32-5p在PCOS大鼠卵巢组织中表达变化及其生物学功能预测
|
摘要
目的探讨miR-32-5p在多囊卵巢综合征(polycystic ovary syndrome,PCOS)大鼠卵巢组织表达变化并预测其可能参与的生物学过程。方法应用脱氢表雄酮(dehydroepiandrosterone,DHEA)颈背部注射建立PCOS大鼠模型;记录大鼠体重、动情周期变化;通过组织病理学观察评估大鼠卵巢形态学变化;应用实时定量PCR检测miR-32-5p在卵巢组织中表达;通过数据库和生物信息学方法预测hsa-miR-32-5p下游靶基因并进行生物学功能分析和信号通路富集分析。结果PCOS组大鼠体重显著增加,动情周期紊乱,卵巢呈多囊样改变;PCOS组大鼠卵巢组织miR-32-5p表达量显著高于对照组;生物信息学分析显示其潜在下游靶基因592个,富集于DNA修复和PI3K-AKT信号通路等生物学调控过程。结论 miR-32-5p在PCOS模型大鼠卵巢组织高表达,可能通过调控下游靶基因影响PCOS病理生理过程。
Objective:To investigate the expression of miR-32-5 p in the ovaries of polycystic ovary syndrome(PCOS)rats induced by dehydroepiandrosterone(DHEA)and predict its biological functions. Methods:PCOS model rats were established by DHEA injection in the neck and back;The body weight was measured and recorded daily;The estrous cycle was evaluated through vaginal smears;A histopathologic study was performed to evaluate morphological changes of ovaries. The expression of miR-32-5 p in ovaries was determined through RT-qPCR;The target genes of hsa-miR-32-5 p and their biological functions and signaling pathways were discovered through database and enrichment analysis. Results:In PCOS rats,the body weight increased significantly,the estrous cycle was disordered and the ovaries showed polycystic morphological changes. The expression of miR-32-5 p was significantly upregulated in ovaries of PCOS rats. 592 target genes were discovered by the intersection of 4 databases.The target genes were enriched in biological processes such as DNA repair and PI3 K-AKT signaling pathway. Conclusion:Our results indicate that the upregulation of miR-32-5 p may affect the pathophysiological process of PCOS via regulating downstream target genes.
Objective:To investigate the expression of miR-32-5 p in the ovaries of polycystic ovary syndrome(PCOS)rats induced by dehydroepiandrosterone(DHEA)and predict its biological functions. Methods:PCOS model rats were established by DHEA injection in the neck and back;The body weight was measured and recorded daily;The estrous cycle was evaluated through vaginal smears;A histopathologic study was performed to evaluate morphological changes of ovaries. The expression of miR-32-5 p in ovaries was determined through RT-qPCR;The target genes of hsa-miR-32-5 p and their biological functions and signaling pathways were discovered through database and enrichment analysis. Results:In PCOS rats,the body weight increased significantly,the estrous cycle was disordered and the ovaries showed polycystic morphological changes. The expression of miR-32-5 p was significantly upregulated in ovaries of PCOS rats. 592 target genes were discovered by the intersection of 4 databases.The target genes were enriched in biological processes such as DNA repair and PI3 K-AKT signaling pathway. Conclusion:Our results indicate that the upregulation of miR-32-5 p may affect the pathophysiological process of PCOS via regulating downstream target genes.
引文
[1]Goodarzi MO,Dumesic DA,Chazenbalk G,et al. Polycystic ovary syndrome:etiology,pathogenesis and diagnosis[J].Nature Reviews Endocrinology,2011,7(4):219-231.
[2]Chan JL,Kar S,Vanky E,et al. Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome:a regional cross-sectional study[J].American Journal of Obstetrics and Gynecology,2017,217(2):189 e181-189 e188.
[3]Ambros V. microRNAs:tiny regulators with great potential[J].Cell,2001,107(7):823-826.
[4]Sirotkin AV,Laukova M,Ovcharenko D,et al. Identification of microRNAs controlling human ovarian cell proliferation and apoptosis[J].J Cell Physiol,2010,223(1):49-56.
[5]Battaglia R,Vento M E,Borzi P,et al. Non-coding RNAs in the Ovarian Follicle[J].Frontiers in Genetics,2017,8:57.
[6]Rosenfield RL,Ehrmann DA.The Pathogenesis of Polycystic Ovary Syndrome(PCOS):The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited[J].Endocr Rev,2016,37(5):467-520.
[7]Ilie IR. Advances in PCOS Pathogenesis and ProgressionMitochondrial Mutations and Dysfunction[J].Advances in Clinical Chemistry,2018,86:127-155.
[8]Lin L,Du T,Huang J,et al. Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance[J].Chin Med J(Engl),2015,128(2):169-174.
[9]Celik L S,Kuyucu Y,Yenilmez E D,et al. Effects of vitamin D on ovary in DHEA-treated PCOS rat model:A light and electron microscopic study[J].Ultrastructural Pathology,2018,42(1):55-64.
[10] Liu S,Zhang X,Shi C,et al.Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome[J].J Transl Med,2015,13:238.
[11] Liu HY,Huang YL,Liu JQ,et al.Transcription factormicro RNA synergistic regulatory network revealing the mechanism of polycystic ovary syndrome[J].Mol Med Rep,2016,13(5):3920-3928.
[12] Li T,Mo H,Chen W,et al. Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome[J].Reprod Sci,2017,24(5):646-655.
[13] Shah K N,Patel S S. Phosphatidylinositide 3-kinase inhibition:A new potential target for the treatment of polycystic ovarian syndrome[J].Pharm Biol,2016,54(6):975-983.
[2]Chan JL,Kar S,Vanky E,et al. Racial and ethnic differences in the prevalence of metabolic syndrome and its components of metabolic syndrome in women with polycystic ovary syndrome:a regional cross-sectional study[J].American Journal of Obstetrics and Gynecology,2017,217(2):189 e181-189 e188.
[3]Ambros V. microRNAs:tiny regulators with great potential[J].Cell,2001,107(7):823-826.
[4]Sirotkin AV,Laukova M,Ovcharenko D,et al. Identification of microRNAs controlling human ovarian cell proliferation and apoptosis[J].J Cell Physiol,2010,223(1):49-56.
[5]Battaglia R,Vento M E,Borzi P,et al. Non-coding RNAs in the Ovarian Follicle[J].Frontiers in Genetics,2017,8:57.
[6]Rosenfield RL,Ehrmann DA.The Pathogenesis of Polycystic Ovary Syndrome(PCOS):The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited[J].Endocr Rev,2016,37(5):467-520.
[7]Ilie IR. Advances in PCOS Pathogenesis and ProgressionMitochondrial Mutations and Dysfunction[J].Advances in Clinical Chemistry,2018,86:127-155.
[8]Lin L,Du T,Huang J,et al. Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance[J].Chin Med J(Engl),2015,128(2):169-174.
[9]Celik L S,Kuyucu Y,Yenilmez E D,et al. Effects of vitamin D on ovary in DHEA-treated PCOS rat model:A light and electron microscopic study[J].Ultrastructural Pathology,2018,42(1):55-64.
[10] Liu S,Zhang X,Shi C,et al.Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome[J].J Transl Med,2015,13:238.
[11] Liu HY,Huang YL,Liu JQ,et al.Transcription factormicro RNA synergistic regulatory network revealing the mechanism of polycystic ovary syndrome[J].Mol Med Rep,2016,13(5):3920-3928.
[12] Li T,Mo H,Chen W,et al. Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome[J].Reprod Sci,2017,24(5):646-655.
[13] Shah K N,Patel S S. Phosphatidylinositide 3-kinase inhibition:A new potential target for the treatment of polycystic ovarian syndrome[J].Pharm Biol,2016,54(6):975-983.