您的位置：山东大学 -> 科技期刊社 -> 《山东大学学报（医学版）》

山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (3): 76-82.doi: 10.6040/j.issn.1671-7554.0.2021.0660

• • 上一篇    

LncRNA-UCA1通过靶向调控miR-182-5p对滋养细胞侵袭与转移的影响

钟黎黎1,盛莹1,郭江虹1,阳双健1,何宜静2   

  • 发布日期:2022-03-09
  • 通讯作者: 盛莹. E-mail:lili841114@126.com
  • 基金资助:
    湖南省卫生健康委2019年度科研计划科研项目(B2019116)

LncRNA-UCA1 effects invasion and metastasis of trophoblast cells by targeting miR-182-5p

ZHONG Lili1, SHENG Ying1, GUO Jianghong1, YANG Shuangjian1, HE Yijing2   

  1. 1. The First Affiliated Hospital, Department of Obstetrics, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China;
    2. The Second Affiliated Hospital, Department of Obstetrics and Gynecology, Hengyang Medical School, University of South China, Hengyang 421001, Hunan, China
  • Published:2022-03-09

PDF (PC)

170

摘要： 目的 探讨长链非编码RNA尿道上皮癌相关基因1(LncRNA-UCA1)对滋养细胞侵袭与转移的影响及其可能机制。 方法 收集30例行剖宫产分娩的子痫前期(PE)患者胎盘组织和30例正常妊娠孕妇胎盘组织,qRT-PCR检测各胎盘组织中UCA1和miR-182-5p表达水平。以滋养细胞HTR-8/Svneo为研究对象,将UCA1过表达质粒(pcDNA3.1-UCA1)及其空载质粒(Vector)转染至细胞中,qRT-PCR检测细胞中UCA1和miR-182-5p表达水平;采用双荧光素酶报告基因实验验证UCA1与miR-182-5p之间的靶向调控关系。将pcDNA3.1-UCA1质粒与miR-182-5p mimic分别或同时转染至HTR-8/Svneo细胞中,CCK-8检测细胞增殖活性;Transwell实验检测细胞侵袭与转移;Western blotting检测基质金属蛋白酶-2(MMP-2)和MMP-9蛋白表达变化。 结果 (1)临床标本测定结果:与正常妊娠孕妇胎盘组织比较,PE患者胎盘组织中UCA1表达降低(1.10±0.51 vs 5.74±1.63),差异有统计学意义(t =14.947,P<0.001),而miR-182-5p表达显著增加(7.23±1.44 vs 1.07±0.72),差异有统计学意义(t=20.961,P<0.001)。(2)细胞实验结果:UCA1能特异性靶向调控miR-182-5p表达。与Vector组比较,UCA1过表达可降低HTR-8/SVneo细胞中miR-182-5p表达(0.12±0.05 vs 0.97±0.06,t=19.028,P<0.001),促进细胞增殖、侵袭和迁移(t=10.160、17.228、13.768,P均<0.001),并上调MMP-2和MMP-9蛋白表达(t=20.833、24.793,P均<0.001);而miR-182-5p过表达能显著减弱UCA1过表达对HTR-8/SVneo细胞增殖、侵袭和迁移的促进作用。 结论 UCA1通过靶向下调miR-182-5p表达促进滋养细胞侵袭与转移。

关键词: 长链非编码RNA, 尿道上皮癌相关基因1, 子痫前期, 滋养细胞, 侵袭, 转移

Abstract: Objective To investigate the effect of long non-coding RNA urethelial carcinoma related gene 1(LncRNA-UCA1)on invasion and metastasis of trophoblast cells and its possible mechanism. Methods Thirty placentas tissues from patients with preeclampsia(PE)and other 30 normal placentas tissues were collected respectively. The expression levels of UCA1 and miR-182-5p in placentas tissues were detected by qRT-PCR. UCA1 overexpression plasmid(pcDNA3.1-UCA1)and its negative plasmid(Vector)were transfected into HTR-8/Svneo cells respectively, and the expression levels of UCA1 and miR-182-5p in cells were detected by qRT-PCR. The targeted regulatory relationship between UCA1 and miR-182-5p was verified by dual-luciferase reporter assay. HTR-8/Svneo cells were transfected with pcDNA3.1-UCA1 plasmid and miR-182-5p mimic respectively or simultaneously, and then cell proliferation activity was detected by CCK-8. Cell invasion and metastasis was detected by Transwell assay. The expression levels of matrix metalloproteinase(MMP)-2 and MMP-9 proteins were detected by Western blotting. Results (1) Results of clinical specimen determination: compared with the placental tissues of normal pregnant women, the expression of UCA1 in placental tissues of PE patients was significantly decreased(1.10±0.51 vs 5.74±1.63, t=14.947, P<0.001), while the expression of miR-182-5p was significantly increased(7.23±1.44 vs 1.07±0.72, t=20.961,P<0.001). (2) Results of cell experiment: UCA1 could specifically target and regulate miR-182-5p expression. Compared with the Vector group, overexpression of UCA1 decreased the expression level of miR-182-5p in HTR-8/SVneo cells(0.12±0.05 vs 0.97±0.06, t=19.028, P<0.001), promoted the proliferation, invasion and migration of HTR-8/SVneo cells(t=10.160, 17.228, 13.768, all P<0.001), and up-regulated the expressions of MMP-2 and MMP-9 protein(t=20.833, 24.793, both P<0.001). However, the overexpression of miR-182-5p significantly reduced the promotion of UCA1 overexpression on the proliferation, invasion and migration of HTR-8/SVneo cells. Conclusion UCA1 promotes trophoblast invasion and metastasis by targeting the down-regulation of miR-182-5p.

Key words: Long non-coding RNA, Urethelial carcinoma related gene 1, Preeclampsia, Trophoblast cell, Invasion, Metastasis

中图分类号: 

  • R714
[1] Macuácua S, Catalão R, Sharma S, et al. Policy review on the management of pre-eclampsia and eclampsia by community health workers in Mozambique[J]. Hum Resour Health, 2019, 17(1): 15.
[2] Burton GJ, Redman CW, Roberts JM, et al. Pre-eclampsia: pathophysiology and clinical implications[J]. BMJ, 2019, 366: l2381. doi: 10.1136/bmj.l2381.
[3] McClements L, Richards C, Patel N, et al. Impact of reduced uterine perfusion pressure model of preeclampsia on metabolism of placenta, maternal and fetal hearts[J]. Sci Rep, 2022, 12(1): 1111.
[4] Kawasaki K, Kondoh E, Chigusa Y, et al. Metabolomic profiles of placenta in preeclampsia[J]. Hypertension, 2019, 73(3): 671-679.
[5] Kim GS, Hwang KA, Choi KC. A promising therapeutic strategy for metastatic gestational trophoblastic disease: engineered anticancer gene-expressing stem cells to selectively target choriocarcinoma[J]. Oncol Lett, 2019, 17(3): 2576-2582.
[6] 李思维, 庞达. 长链非编码RNA(lncRNA)在癌症中的作用[J]. 实用肿瘤学杂志, 2019, 33(5): 471-475. LI Siwei, PANG Da. Long non-coding RNA(lncRNA)role in cancer [J]. Practical Oncology Journal, 2019, 33(5): 471-475.
[7] Khawar MB, Hamid SE, Jan T, et al. Diagnostic, prognostic and therapeutic potential of long noncoding RNAs in cancer[J]. Mol Biol Rep, 2022. doi: 10.1007/s11033-022-07180-z.
[8] Wang F, Li X, Xie XJ, et al. UCA1, a non-protein-coding RNA up-regulated in bladder carcinoma and embryo, influencing cell growth and promoting invasion[J]. FEBS Lett, 2008, 582(13): 1919-1927.
[9] Yao F, Wang Q, Wu Q. The prognostic value and mechanisms of lncRNA UCA1 in human cancer[J]. Cancer Manag Res, 2019, 11: 7685-7696. doi: 10.2147/CMAR.S200436.
[10] Fang YN, Huang ZL, Li H, et al. Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion[J]. Eur Rev Med Pharmacol Sci, 2018, 22(20): 6583-6590.
[11] Abu-Dief EE, Elsayed HM, Atia EW, et al. Modulation of telocytes in women with preeclampsia: a prospective comparative study[J]. J Microsc Ultrastruct, 2021, 9(4): 158-163.
[12] Ibanoglu MC, Oskovi-Kaplan ZA, Ozgu-Erdinc AS, et al. Comparison of the Kisspeptin levels in early onset preeclampsia and late-onset preeclampsia[J]. Arch Gynecol Obstet, 2022. doi: 10.1007/s00404-021-06359-2.
[13] 吴秋雨,郇金亮. 颗粒蛋白前体通过调控滋养层细胞的侵袭和凋亡影响子痫前期发病[J]. 第三军医大学学报, 2018, 40(20): 1858-1864. WU Qiuyu, HUAN Jinliang. Progranulin may suppress preeclampsia by promoting invasion and apoptosis of trophoblast cells [J]. Acta Academiae Medicinae Militaris Tertiae, 2018, 40(20): 1858-1864.
[14] Song X, Luo X, Gao Q, et al. Dysregulation of lncRNAs in placenta and pathogenesis of preeclampsia[J]. Curr Drug Targets, 2017, 18(10): 1165-1170.
[15] Munjas J, Sopi c M, Stefanovi c A, et al. Non-coding RNAs in preeclampsia-molecular mechanisms and diagnostic potential[J]. Int J Mol Sci, 2021, 22(19): 10652.
[16] Sun N, Qin S, Zhang L, et al. Roles of noncoding RNAs in preeclampsia[J]. Reprod Biol Endocrinol, 2021, 19(1): 100.
[17] He X, He Y, Xi B, et al. LncRNAs expression in preeclampsia placenta reveals the potential role of LncRNAs contributing to preeclampsia pathogenesis[J]. PLoS One, 2013, 8(11): e81437.
[18] 刘沙沙,左俊芳,崔洪艳.长链非编码RNA与子痫前期相关机制的研究进展[J].国际妇产科学杂志, 2018, 45(3): 250-253. LIU Shasha, ZUO Junfang, CUI Hongyan. Advances in the association between LncRNAs and preeclampsia [J]. Guoji Fuchankexue Zazhi, 2018, 45(3): 250-253.
[19] Sun MD, Zheng YQ, Wang LP, et al. Long noncoding RNA UCA1 promotes cell proliferation, migration and invasion of human leukemia cells via sponging miR-126[J]. Eur Rev Med Pharmacol Sci, 2018, 22(8): 2233-2245.
[20] Fang Q, Chen X, Zhi X. Long non-coding RNA(LncRNA)urothelial carcinoma associated 1(UCA1)increases multi-drug resistance of gastric cancer via downregulating miR-27b[J]. Med Sci Monit, 2016, 22: 3506-3513. doi: 10.12659/msm.900688.
[21] Fang YN, Huang ZL, Li H, et al. Highly expressed miR-182-5p can promote preeclampsia progression by degrading RND3 and inhibiting HTR-8/SVneo cell invasion[J]. Eur Rev Med Pharmacol Sci, 2018, 22(20): 6583-6590.
[22] Zhang M, Zhao Y, Zhang Y, et al. LncRNA UCA1 promotes migration and invasion in pancreatic cancer cells via the Hippo pathway[J]. Biochim Biophys Acta Mol Basis Dis, 2018, 1864(5 Pt A): 1770-1782.
[23] Xie F, Li Y, Wang M, et al. Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis[J]. Mol Cancer, 2018, 17(1): 144.
[24] 丰琳,李炎.子痫前期产妇血清MMP2、MMP9含量检测及胎盘床血流动力学异常情况评估[J].海南医学院学报, 2015, 21(1): 111-113. FENG Lin, LI Yan. MMP2, MMP9 content in preeclampsia maternal serum and placental bed hemodynamic abnormality evaluation [J]. Journal of Hainan Medical University, 2015, 21(1): 111-113.
[25] Zhang SM, Tian FJ, Zeng WH, et al. XCL1-XCR1 pathway promotes trophoblast invasion at maternal-fetal interface by inducing MMP-2/MMP-9 activity[J]. Am J ReprodImmunol, 2018, 80(3): e12990.
[26] Plaks V, Rinkenberger J, Dai J, et al. Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction[J]. Proc Natl Acad Sci U S A, 2013, 110(27): 11109-11114.
[1] 乔宠,王婷婷. 母胎免疫调节机制的研究进展[J]. 山东大学学报 (医学版), 2021, 59(8): 24-31.
[2] 褚晏,刘端瑞,朱文帅,樊荣,马晓丽,汪运山,郏雁飞. DNA甲基化转移酶在胃癌中的表达及其临床意义[J]. 山东大学学报 (医学版), 2021, 59(7): 1-9.
[3] 李皖皖,周文凯,董书晴,贺士卿,刘钊,张家新,刘斌. 利用数据库信息构建乳腺癌免疫关联lncRNAs风险评估模型[J]. 山东大学学报 (医学版), 2021, 59(7): 74-84.
[4] 孔雪,李娟,段伟丽,史爽,李培龙,杜鲁涛,毛海婷,王传新. 长链非编码RNA AC012073.1对乳腺癌细胞迁移侵袭的影响及临床价值[J]. 山东大学学报 (医学版), 2021, 59(4): 70-78.
[5] 柴佳威,朱坤兵,张华伟,崔凤云,王甜甜,田兴松. 1例肝细胞肝癌甲状腺转移罕见病例报道与文献回顾[J]. 山东大学学报 (医学版), 2021, 59(3): 120-124.
[6] 高金梅,张向莲,刘铁菊. 血浆D-二聚体与109例膀胱癌中发生31例转移的关联性分析[J]. 山东大学学报 (医学版), 2021, 59(3): 98-102.
[7] 李灿楦,陈洁. 基于生物信息学分析乙酰辅酶A酰基转移酶1在肾透明细胞癌中的表达及作用机制[J]. 山东大学学报 (医学版), 2021, 59(2): 26-33.
[8] 薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.
[9] 陈国丹,周勤,刘治玲,李福艳,朱庆章,于永梅,曾庆师. 6例盆腔侵袭性血管粘液瘤影像特征[J]. 山东大学学报 (医学版), 2021, 59(2): 55-59.
[10] 杜甜甜,李娟,赵颖慧,段伟丽,王景,王允山,杜鲁涛,王传新. 长链非编码RNA LINC02474在结直肠癌中的表达特征及对细胞增殖的影响[J]. 山东大学学报 (医学版), 2021, 59(10): 57-67.
[11] 孙薏丰,高玉,梁永媛,高杨. CPLX2在30例肝癌组织的表达及其对体外细胞增殖与侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(9): 34-39.
[12] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38-46.
[13] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 32-37.
[14] 史丽,马静,赵喜娃,关英霞,赵连梅,单保恩. miR-25-3p在40例子宫内膜腺癌组织中的表达及对KLE细胞生物学功能的影响[J]. 山东大学学报 (医学版), 2020, 58(12): 86-91.
[15] 李昌达,史永军,林彦良. 27-羟基胆固醇与胆固醇对裸鼠食管鳞癌和人食管癌细胞增殖的影响[J]. 山东大学学报 (医学版), 2020, 58(11): 45-52.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
版权所有 © 2018 《山东大学学报(医学版)》编辑部　
地址:山东大学科技期刊社（济南市历城区山大南路27号山东大学中心校区明德楼B座721室） 电话: 0531-88366918 E-mail: xbyxb@sdu.edu.cn
本系统由北京玛格泰克科技发展有限公司设计开发