受孕激素调节的microRNAs与乳腺癌的关系

doi:10.3969/j.issn.1006-7795.2017.04.007

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (4): 521-525.doi: 10.3969/j.issn.1006-7795.2017.04.007

受孕激素调节的microRNAs与乳腺癌的关系

王利娟¹, 杨春², 谷牧青³, Pierre Hardy², 阮祥燕^1,4, Alfred O. Mueck^1,4

1. 首都医科大学附属北京妇产医院妇科内分泌科, 北京 100026;
2. 蒙特利尔大学药理系圣贾斯汀医院研究中心, 蒙特利尔 H3T 1C5, 加拿大;
3. 首都医科大学附属北京妇产医院生殖医学科, 北京 100026;
4. 德国图宾根大学妇产医院绝经内分泌中心, 图宾根 D-72076, 德国

收稿日期:2017-06-05 出版日期:2017-07-21 发布日期:2017-07-20
通讯作者: 阮祥燕 E-mail:ruanxiangyan@163.com
基金资助:
国家自然科学基金（81671411），国家外国专家局2017年度北京市引进国外技术、管理人才项目（20171100004），北京市自然科学基金（7162062），北京市科技新星计划交叉学科合作项目（Z161100004916045），北京市卫生系统高层次卫生技术人才（学科带头人）（2014-2-016）

Relationship between progesterone-regulated microRNAs and breast cancer

Wang Lijuan¹, Yang Chun², Gu Muqing³, Pierre Hardy², Ruan Xiangyan^1,4, Alfred O. Mueck^1,4

1. Department of Gynecological Endocrinology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
2. Research Center of CHU-saint-Justine Hospital, Pharmacology Department, University of Montreal, Montreal H3T 1C5, Canada;
3. Department of Reproduction, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China;
4. Section of Endocrinology and Menopause, Department of Women's Health, University of Tubingen, Tubingen D-72076, Germany

Received:2017-06-05 Online:2017-07-21 Published:2017-07-20
Supported by:
This study was supported by National Natural Science Foundation of China(81671411), Foreign Technical and Administrative Talent Introduction Project in 2017, State Administration of Foreign Experts Affairs, China(20171100004); Natural Science Foundation of Beijing (7162062);Beijing Nova Program Interdisciplinary Studies Cooperative Projects (Z161100004916045); Beijing Municipal Health System High Level Health Technical Talents (Academic Leaders)(2014-2-016)

摘要/Abstract

摘要： microRNAs（miRNAs）是一类小的非编码RNAs，在转录后水平调节多细胞真核生物基因的表达。miRNA突变或异常表达与各种人类癌症相关，并且可作为肿瘤抑制因子和致癌基因发挥作用。孕激素受体（progesterone receptor，PR）介导正常乳腺和乳腺癌组织对孕激素的应答。孕激素暴露是绝经后乳腺癌的一个公认风险因素，尤其是合成孕激素。研究结果表明激素调节的miRNAs在激素受体介导的基因调控中起重要作用，受孕激素调节的miRNAs可影响孕激素受体的表达及其活动。因此，未来应该深入研究孕激素、孕激素受体和miRNAs关系的基因调控和分子机制，就miRNA对乳腺癌诊断、治疗和预后的潜力进行深入评估。

关键词: 乳腺癌, 孕激素, 孕激素受体, microRNAs, 基因调控, 分子机制

Abstract: microRNAs(miRNAs) are a class of small non-coding RNAs that regulate the expression of multicellular eukaryotic genes at post-transcriptional levels. miRNA mutations or abnormal expressions are associated with various human cancers. miRNAs can function as tumour suppressors and oncogenes. Progesterone receptors (PR) mediate response to progestins in the normal breast and breast cancer. Progesterone exposure is a recognized risk factor for postmenopausal breast cancer, especially synthetic progesterone. Several studies have shown that hormonal regulated miRNAs have an important role in hormone receptor mediated gene regulation. Progesterone regulated miRNAs can affect the expression of progesterone receptors and their activities. Therefore, further studies are needed to dissect the gene regulations and molecular mechanisms related to progestine, PR and miRNAs. The diagnostic, therapeutic and prognostic potential of these miRNAs in breast cancer should be further evaluated.

Key words: breast cancer, progesterone, progeterone receptor, microRNAs, gene regulation, molecular mechanisms

中图分类号:

R737.9

王利娟, 杨春, 谷牧青, Pierre Hardy, 阮祥燕, Alfred O. Mueck. 受孕激素调节的microRNAs与乳腺癌的关系[J]. 首都医科大学学报, 2017, 38(4): 521-525.

Wang Lijuan, Yang Chun, Gu Muqing, Pierre Hardy, Ruan Xiangyan, Alfred O. Mueck. Relationship between progesterone-regulated microRNAs and breast cancer[J]. Journal of Capital Medical University, 2017, 38(4): 521-525.

参考文献

[1] Manne R K, Agrawal Y, Bargale A, et al. A microRNA/ubiquitin ligase feedback loop regulates slug-mediated invasion in breast cancer[J]. Neoplasia, 2017, 19(6):483-495.
[2] Zhang B, Pan X, Cobb GP, et al. microRNAs as oncogenes and tumor suppressors[J]. Dev Biol, 2007, 302(1):1-12.
[3] Filipowicz W, Bhattacharyya S N, Sonenberg N, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?[J].Nat Rev Genet,2008,9(2):102-114.
[4] Krol J, Loedige I, Filipowicz W. The widespread regulaton of microRNA biogenesis, function and decay[J]. Nat Rev Genet, 2010, 11(9):597-610.
[5] Melo S A, Esteller M. Dysregulation of microRNAs in cancer: playing with fire[J]. FEBS Lett, 2011,585(13):2087-2099.
[6] Babashah S, Soleimani M. The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis[J].Eur J Cancer, 2011,47(8):1127-1137.
[7] Jansson M D, Lund A H. MicroRNA and cancer[J]. Mol Oncol,2012,6(6):590-610.
[8] Neubauer H, Chen R, Schneck H, et al. New insight on a possible mechanism of progestogens in terms of breast cancer risk[J]. Horm Mol Biol Clin Investig, 2011, 6(1):185-192.
[9] Zhang Y, Ruan X, Willibald M, et al. May progesterone receptor membrane component 1 (PGRMC1) predict the risk of breast cancer?[J]. Gynecol Endocrinol, 2016, 32(1):58-60.
[10] Ruan X, Zhang Y, Mueck A O, et al. Increased expression of progesterone receptor membrane component 1 is associated with aggressive phenotype and poor prognosis in ER-positive and negative breast cancer[J]. Menopause, 2017, 24(2):203-209.
[11] Bardou V J, Arpino G, Elledge R M, et al. Progesterone receptor status signifcantly improves outcome prediction over estrogen receptor status alone for adjuvant endocrine therapy in two large breast cancer databases[J]. J Clin Oncol, 2003, 21(10):1973-1979.
[12] Colozza M, Larsimont D, Piccart M J. Progesterone receptor testing: not the right time to be buried[J]. J Clin Oncol, 2005, 23(16):3867-3868.
[13] Fernö M, Stål O, Baldetorp B, et al. Results of two or five years of adjuvant tamoxifen correlated to steroid receptor and S-phase levels. South Sweden Breast Cancer Group, and South-East Sweden Breast Cancer Group[J]. Breast Cancer Res Treat, 2000, 59(1):69-76.
[14] Kuokkanen S, Chen B, Ojalvo L, et al. Genomic profling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium[J]. Biol Reprod, 2010, 82(4):791-801.
[15] Xia H F, Jin X H, Song P P, et al. Temporal and spatial regulation of let-7a in the uterus during embryo implantation in the rat[J]. J Reprod Dev, 2010, 56(1):73-78.
[16] Xia H F, Jin X H, Song P P, et al. Temporal and spatial regulation of miR-320 in the uterus during embryo implantation in the rat[J]. Int J Mol Sci, 2010, 11(2):719-730.
[17] Silveri L, Tilly G, Vilotte J L, et al. MicroRNA involvement in mammary gland development and breast cancer[J]. Reprod Nutr Dev, 2006, 46(5):549-556.
[18] Williams K C, Renthal N E, Condon J C, et al. MicroRNA-200a serves a key role in the decline of progesterone receptor function leading to term and preterm labor[J]. Proc Natl Acad Sci U S A, 2012, 109(19):7529-7534.
[19] Adams B D, Furneaux H, White B A. The micro-ribonucleic acid (miRNA) miR-206 targets the human estrogen receptor-alpha (ERalpha) and represses ERalpha messenger RNA and protein expression in breast cancer cell lines[J]. Mol Endocrinol, 2007, 21(5):1132-1147.
[20] Castellano L, Giamas G, Jacob J, et al. The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response[J]. Proc Natl Acad Sci USA, 2009, 106(37):15732-15737.
[21] Pandey D P, Picard D. miR-22 inhibits estrogen signaling by directly targeting the estrogen receptor alpha mRNA[J]. Mol Cell Biol, 2009, 29(13):3783-3790.
[22] Zhao J J, Lin J, Yang H, et al. MicroRNA-221/222 negatively regulates estrogen receptor alpha and is associated with tamoxifen resistance in breast cancer[J]. J Biol Chem, 2008, 283(45):31079-31086.
[23] Cohen A, Shmoish M, Levi L, et al. Alterations in micro-ribonucleic acid expression profiles reveal a novel pathway for estrogen regulation[J]. Endocrinology, 2008, 149(4):1687-1696.
[24] Klinge C M. Estrogen regulation of microRNA expression[J]. Curr Genomics, 2009,10(3): 169-183.
[25] Nothnick W B, Healy C, Hong X. Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1[J]. Endocrine, 2010, 37(2):265-273.
[26] Cizeron-Clairac G, Lallemand F, Vacher S,et al, MiR-190b, the highest up-regulated miRNA in ERα-positive compared to ERα-negative breast tumors, a new biomarker in breast cancers?[J]. BMC Cancer,2015,15:499
[27] Gilam A, Shai A, Ashkenazi I, et al. MicroRNA regulation of progesterone receptor in breast cancer[J]. Oncotarget, 2017, 8(16):25963-25976.
[28] Cochrane D R, Spoelstra N S, Richer J K. The role of miRNAs in progesterone action[J]. Mol Cell Endocrinol,2012,357(1-2):50-59.
[29] Nothnick W B, Healy C,Hong X. Steroidal regulation of uterine miRNAs is associated with modulation of the miRNA biogenesis components Exportin-5 and Dicer1[J]. Endocrine,2010,37(2): 265-273.
[30] Yuan D Z,Yu L L,Qu T, et al.Identification and characterization of progesterone- and estrogen-regulated microRNAs in mouse endometrial epithelial cells[J]. Reprod Sci, 2015,22(2): 223-234.
[31] Cochrane D R, Jacobsen B M, Connaghan K D, et al. Progestin regulated miRNAs that mediate progesterone receptor action in breast cancer[J]. Mol Cell Endocrinol, 2012, 355(1): 15-24.
[32] Finlay-Schultz J, Cittelly D M,Hendricks P,et al. Progesterone downregulation of miR-141 contributes to expansion of stem-like breast cancer cells through maintenance of progesterone receptor and Stat5a[J]. Oncogene, 2015,34(28): 3676-3687.
[33] Cittelly DM, Finlay-Schultz J, Howe E N, et al. Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4[J]. Oncogene, 2013, 32(20): 2555-2564.
[34] Rivas M A, Venturutti L, Huang Y W,et al. Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic signaling contributes to breast cancer development[J]. Breast Cancer Res, 2012, 14(3):R77.
[35] Maillot G, Lacroix-Triki M, Pierredon S, et al. Widespread estrogen dependent repression of micrornas involved in breast tumor cell growth[J]. Cancer Res, 2009, 69(21):8332-8340.
[36] Lange C A. Challenges to defining a role for progesterone in breast cancer[J]. Steroids, 2008, 73(9-10):914-921.
[37] Panda H, Chuang T D, Luo X, et al. Endometrial miR-181a and miR-98 expression is altered during transition from normal into cancerous state and target PGR, PGRMC1, CYP19A1, DDX3X, and TIMP3[J]. J Clin Endocrinol Metab, 2012, 97(7): E1316-1326.
[38] Lu Z, Ye Y, Jiao D, et al. miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status[J]. Oncol Lett, 2012, 4(5): 1027-1032.
[39] Cui W, Li Q, Feng L, et al. MiR-125-3p regulates progesterone receptors and involves development and lactation of mouse mammary gland[J]. Mol Cell Biochem, 2011, 355(1-2):17-25.

受孕激素调节的microRNAs与乳腺癌的关系

Relationship between progesterone-regulated microRNAs and breast cancer

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	赵越, 阮祥燕, 程姣姣, 谷牧青, 许新, 王月姣. 乳腺癌中PGRMC1表达与临床病理参数的相关性[J]. 首都医科大学学报, 2022, 43(3): 350-356.
[2]	魏常胜, 骆成玉, 张树琦. 环乳晕切口联合乳腔镜腋窝淋巴结清扫在早期乳腺癌保乳手术中的应用[J]. 首都医科大学学报, 2021, 42(6): 1014-1020.
[3]	中华预防医学会妇女保健分会; 中国人体健康科技促进会妇科内分泌与生育力促进专委会. 乳腺癌患者选择性雌激素受体调节剂治疗相关子宫内膜安全管理的中国专家共识(2021版)[J]. 首都医科大学学报, 2021, 42(4): 672-677.
[4]	阮祥燕, 杨瑜, 卢丹, 杜娟, 程姣姣, 谷牧青, 李扬璐, 金凤羽, 段微, 代荫梅, 鞠蕊, 许新, MatthiasKorell, AlfredO.Mueck. 中国首例乳腺癌患者冻存卵巢组织移植成功报道及文献复习[J]. 首都医科大学学报, 2021, 42(2): 177-182.
[5]	王璇, 马重阳, 张雅文, 程宏发, 张秋霞. 基于网络药理学的侯氏黑散抗缺血性脑卒中机制研究[J]. 首都医科大学学报, 2021, 42(1): 43-52.
[6]	杨阳, 康骅, 赵菁, 凌煜玮, 赵烨, 王亚军, 戎冬冬. 术前乳腺MRI对乳腺癌保乳手术切缘评估的回顾性分析[J]. 首都医科大学学报, 2020, 41(6): 943-953.
[7]	王婉晴, 靳路远. 坚持是成功的基石——范志朋教授[J]. 首都医科大学学报, 2020, 41(5): 752-755.
[8]	王爱婷, 鄢丹, 齐宪荣. 包载多西他赛的聚合物胶束抑制小鼠乳腺癌转移作用研究[J]. 首都医科大学学报, 2020, 41(2): 225-230.
[9]	王维, 张紫寒, 翟妍, 桑翠琴, 王淑珍. 子宫体、乳腺双原发癌的临床病理特征[J]. 首都医科大学学报, 2019, 40(6): 857-862.
[10]	张蕴显, 王雅梅, 周萍. 乳腺癌中基于开放染色质的环状RNA互作网络构建及功能分析[J]. 首都医科大学学报, 2019, 40(6): 901-910.
[11]	白向东, 郝雅婷, 张欣雪, 贺强. 脾多肽注射液联合术后化疗对三阴性乳腺癌患者临床疗效的研究[J]. 首都医科大学学报, 2019, 40(6): 911-915.
[12]	张凌燕, 阮祥燕, 蔡桂举, 谷牧青, Alfred O. Mueck. 他莫昔芬治疗转染孕激素受体膜组分1乳腺癌裸鼠模型对乳腺肿瘤组织Ki-67表达的影响[J]. 首都医科大学学报, 2019, 40(4): 533-538.
[13]	王月姣, 阮祥燕, 谷牧青, 蔡桂举, 李雪, 张凌燕, Alfred O. Mueck. 他莫昔芬治疗乳腺癌异种移植瘤裸鼠子宫病理改变[J]. 首都医科大学学报, 2019, 40(4): 539-543.
[14]	白向东, 郝雅婷, 张欣雪, 贺强. 雌激素受体阳性和阴性乳腺癌术后辅助化学药物治疗中加用脾多肽的临床免疫疗效观察[J]. 首都医科大学学报, 2019, 40(3): 443-448.
[15]	陈妮娜, 范怡畅, 尚昆, 杨婧, 曹邦伟. 血清血脂及载脂蛋白浓度与乳腺癌分子分型及Ki-67表达水平的相关性研究[J]. 首都医科大学学报, 2019, 40(2): 191-194.