Skip to main content
Top
Published in: Tumor Biology 7/2016

01-07-2016 | Original Article

MiR-381 inhibits epithelial ovarian cancer malignancy via YY1 suppression

Authors: Bairong Xia, Huiyan Li, Shanshan Yang, Tianbo Liu, Ge Lou

Published in: Tumor Biology | Issue 7/2016

Login to get access

Abstract

Epithelial ovarian cancer (EOC) is a common type of gynecologic cancer, which accounts for the majority of deaths among all gynecologic malignant tumors in developed countries. A series of recent studies suggested that miR-381 might play important roles in the development of various cancer types. However, the biological function of miR-381 in EOC remains to be investigated. We examined the levels of miR-381 expression in EOC tissues and cell lines. We identified miR-381 target genes by bioinformatic prediction. We also characterized the phenotype regarding cell proliferation, cell migration, and cell invasion in EOC cells lines with altered expression levels of both miR-381 and its target gene, YY1. The expression levels of miR-381 were downregulated in EOC tissues and cell lines. Overexpression of miR-381 significantly inhibited EOC cell proliferation, migration, and invasion. Restoration of YY1 expression partially reversed the phenotype induced by miR-381 overexpression. Knockdown of miR-381 target gene, YY1, mimicked the phenotype induced by miR-381 overexpression. MiR-381 regulated EOC cell through miR-381/YY1/p53 and miR-381/YY1/Wnt signaling axis. We concluded that miR-381 inhibited EOC cell proliferation, migration, and invasion, at least in part, via suppressing YY1 expression.
Appendix
Available only for authorised users
Literature
1.
go back to reference Granato T, Midulla C, Longo F, Colaprisca B, Frati L, Anastasi E. Role of he4, ca72.4, and ca125 in monitoring ovarian cancer. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2012;33:1335–9.CrossRef Granato T, Midulla C, Longo F, Colaprisca B, Frati L, Anastasi E. Role of he4, ca72.4, and ca125 in monitoring ovarian cancer. Tumour Biol J Int Soc Oncodevelopmental Biol Med. 2012;33:1335–9.CrossRef
2.
go back to reference Bristow RE. Surgical standards in the management of ovarian cancer. Curr Opin Oncol. 2000;12:474–80.CrossRefPubMed Bristow RE. Surgical standards in the management of ovarian cancer. Curr Opin Oncol. 2000;12:474–80.CrossRefPubMed
3.
go back to reference Chang SJ, Bristow RE. Evolution of surgical treatment paradigms for advanced-stage ovarian cancer: redefining 'optimal' residual disease. Gynecol Oncol. 2012;125:483–92.CrossRefPubMed Chang SJ, Bristow RE. Evolution of surgical treatment paradigms for advanced-stage ovarian cancer: redefining 'optimal' residual disease. Gynecol Oncol. 2012;125:483–92.CrossRefPubMed
4.
go back to reference Harter P, Muallem ZM, Buhrmann C, Lorenz D, Kaub C, Hils R, et al. Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer. Gynecol Oncol. 2011;121:615–9.CrossRefPubMed Harter P, Muallem ZM, Buhrmann C, Lorenz D, Kaub C, Hils R, et al. Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer. Gynecol Oncol. 2011;121:615–9.CrossRefPubMed
5.
go back to reference Harries M, Gore M. Part i: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis. Lancet Oncol. 2002;3:529–36.CrossRefPubMed Harries M, Gore M. Part i: chemotherapy for epithelial ovarian cancer-treatment at first diagnosis. Lancet Oncol. 2002;3:529–36.CrossRefPubMed
6.
go back to reference Matei DE, Nephew KP. Epigenetic therapies for chemoresensitization of epithelial ovarian cancer. Gynecol Oncol. 2010;116:195–201.CrossRefPubMed Matei DE, Nephew KP. Epigenetic therapies for chemoresensitization of epithelial ovarian cancer. Gynecol Oncol. 2010;116:195–201.CrossRefPubMed
7.
go back to reference Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microrna biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–34.CrossRefPubMed Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microrna biogenesis pathways and their regulation. Nat Cell Biol. 2009;11:228–34.CrossRefPubMed
8.
go back to reference Osada H, Takahashi T. Micrornas in biological processes and carcinogenesis. Carcinogenesis. 2007;28:2–12.CrossRefPubMed Osada H, Takahashi T. Micrornas in biological processes and carcinogenesis. Carcinogenesis. 2007;28:2–12.CrossRefPubMed
9.
go back to reference Zhang Q, Tang Q, Qin D, Yu L, Huang R, Lv G, et al. Role of microrna 30a targeting insulin receptor substrate 2 in colorectal tumorigenesis. Mol Cell Biol. 2015;35:988–1000.CrossRefPubMedPubMedCentral Zhang Q, Tang Q, Qin D, Yu L, Huang R, Lv G, et al. Role of microrna 30a targeting insulin receptor substrate 2 in colorectal tumorigenesis. Mol Cell Biol. 2015;35:988–1000.CrossRefPubMedPubMedCentral
10.
go back to reference Sui X, Wang X, Han W, Li D, Xu Y, Lou F, et al. Micrornas-mediated cell fate in triple negative breast cancers. Cancer Lett. 2015;361:8–12.CrossRefPubMed Sui X, Wang X, Han W, Li D, Xu Y, Lou F, et al. Micrornas-mediated cell fate in triple negative breast cancers. Cancer Lett. 2015;361:8–12.CrossRefPubMed
12.
go back to reference Lee SH, Jung YD, Choi YS, Lee YM. Targeting of runx3 by mir-130a and mir-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. Oncotarget. 2015. Lee SH, Jung YD, Choi YS, Lee YM. Targeting of runx3 by mir-130a and mir-495 cooperatively increases cell proliferation and tumor angiogenesis in gastric cancer cells. Oncotarget. 2015.
13.
go back to reference Guo M, Zhang X, Wang G, Sun J, Jiang Z, Khadarian K, et al. Mir-603 promotes glioma cell growth via wnt/beta-catenin pathway by inhibiting wif1 and ctnnbip1. Cancer Lett. 2015;360:76–86.CrossRefPubMed Guo M, Zhang X, Wang G, Sun J, Jiang Z, Khadarian K, et al. Mir-603 promotes glioma cell growth via wnt/beta-catenin pathway by inhibiting wif1 and ctnnbip1. Cancer Lett. 2015;360:76–86.CrossRefPubMed
14.
go back to reference Liu YN, Yin J, Barrett B, Sheppard-Tillman H, Li D, Casey OM, et al. Loss of androgen-regulated microrna 1 activates src and promotes prostate cancer bone metastasis. Mol Cell Biol. 2015;35:1940–51.CrossRefPubMedPubMedCentral Liu YN, Yin J, Barrett B, Sheppard-Tillman H, Li D, Casey OM, et al. Loss of androgen-regulated microrna 1 activates src and promotes prostate cancer bone metastasis. Mol Cell Biol. 2015;35:1940–51.CrossRefPubMedPubMedCentral
15.
go back to reference Li X, Li H, Zhang R, Liu J. Microrna-449a inhibits proliferation and induces apoptosis by directly repressing e2f3 in gastric cancer. Cell Physiol Biochem Int J Exp Cell Physiol, Biochem Pharmacol. 2015;35:2033–42.CrossRef Li X, Li H, Zhang R, Liu J. Microrna-449a inhibits proliferation and induces apoptosis by directly repressing e2f3 in gastric cancer. Cell Physiol Biochem Int J Exp Cell Physiol, Biochem Pharmacol. 2015;35:2033–42.CrossRef
16.
go back to reference Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, et al. Interaction of hsa-mir-381 and glioma suppressor lrrc4 is involved in glioma growth. Brain Res. 2011;1390:21–32.CrossRefPubMed Tang H, Liu X, Wang Z, She X, Zeng X, Deng M, et al. Interaction of hsa-mir-381 and glioma suppressor lrrc4 is involved in glioma growth. Brain Res. 2011;1390:21–32.CrossRefPubMed
17.
go back to reference Liang Y, Zhao Q, Fan L, Zhang Z, Tan B, Liu Y, et al. Down-regulation of microrna-381 promotes cell proliferation and invasion in colon cancer through up-regulation of lrh-1. Biomed Pharmacother Biomed Pharmacotherapie. 2015;75:137–41.CrossRef Liang Y, Zhao Q, Fan L, Zhang Z, Tan B, Liu Y, et al. Down-regulation of microrna-381 promotes cell proliferation and invasion in colon cancer through up-regulation of lrh-1. Biomed Pharmacother Biomed Pharmacotherapie. 2015;75:137–41.CrossRef
18.
go back to reference Rothschild SI, Tschan MP, Jaggi R, Fey MF, Gugger M, Gautschi O. Microrna-381 represses id1 and is deregulated in lung adenocarcinoma. J Thorac Oncol : Off Publ Int Assoc Study Lung Cancer. 2012;7:1069–77.CrossRef Rothschild SI, Tschan MP, Jaggi R, Fey MF, Gugger M, Gautschi O. Microrna-381 represses id1 and is deregulated in lung adenocarcinoma. J Thorac Oncol : Off Publ Int Assoc Study Lung Cancer. 2012;7:1069–77.CrossRef
19.
go back to reference Chen B, Liu B. [mirna-381 inhibits the invasion of renal carcinoma and the underlying mechanisms]. Zhong nan da xue xue bao Yi xue ban J Cent South Univ Med Sci. 2015;40:1053–9. Chen B, Liu B. [mirna-381 inhibits the invasion of renal carcinoma and the underlying mechanisms]. Zhong nan da xue xue bao Yi xue ban J Cent South Univ Med Sci. 2015;40:1053–9.
20.
go back to reference Chen B, Duan L, Yin G, Tan J, Jiang X. Simultaneously expressed mir-424 and mir-381 synergistically suppress the proliferation and survival of renal cancer cells—cdc2 activity is up-regulated by targeting wee1. Clinics. 2013;68:825–33.CrossRefPubMedPubMedCentral Chen B, Duan L, Yin G, Tan J, Jiang X. Simultaneously expressed mir-424 and mir-381 synergistically suppress the proliferation and survival of renal cancer cells—cdc2 activity is up-regulated by targeting wee1. Clinics. 2013;68:825–33.CrossRefPubMedPubMedCentral
21.
go back to reference Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y. Targeted disruption of mouse yin yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol. 1999;19:7237–44.CrossRefPubMedPubMedCentral Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y. Targeted disruption of mouse yin yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol. 1999;19:7237–44.CrossRefPubMedPubMedCentral
22.
go back to reference Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by yy1, a human gli-kruppel-related protein, and relief of repression by adenovirus e1a protein. Cell. 1991;67:377–88.CrossRefPubMed Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by yy1, a human gli-kruppel-related protein, and relief of repression by adenovirus e1a protein. Cell. 1991;67:377–88.CrossRefPubMed
23.
go back to reference Gordon S, Akopyan G, Garban H, Bonavida B. Transcription factor yy1: structure, function, and therapeutic implications in cancer biology. Oncogene. 2006;25:1125–42.CrossRefPubMed Gordon S, Akopyan G, Garban H, Bonavida B. Transcription factor yy1: structure, function, and therapeutic implications in cancer biology. Oncogene. 2006;25:1125–42.CrossRefPubMed
25.
go back to reference Sui G, el Affar B, Shi Y, Brignone C, Wall NR, Yin P, et al. Yin yang 1 is a negative regulator of p53. Cell. 2004;117:859–72.CrossRefPubMed Sui G, el Affar B, Shi Y, Brignone C, Wall NR, Yin P, et al. Yin yang 1 is a negative regulator of p53. Cell. 2004;117:859–72.CrossRefPubMed
26.
go back to reference Yakovleva T, Kolesnikova L, Vukojevic V, Gileva I, Tan-No K, Austen M, et al. Yy1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription. Biochem Biophys Res Commun. 2004;318:615–24.CrossRefPubMed Yakovleva T, Kolesnikova L, Vukojevic V, Gileva I, Tan-No K, Austen M, et al. Yy1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription. Biochem Biophys Res Commun. 2004;318:615–24.CrossRefPubMed
27.
go back to reference Yokoyama NN, Pate KT, Sprowl S, Waterman ML. A role for yy1 in repression of dominant negative lef-1 expression in colon cancer. Nucleic Acids Res. 2010;38:6375–88.CrossRefPubMedPubMedCentral Yokoyama NN, Pate KT, Sprowl S, Waterman ML. A role for yy1 in repression of dominant negative lef-1 expression in colon cancer. Nucleic Acids Res. 2010;38:6375–88.CrossRefPubMedPubMedCentral
28.
go back to reference Zhang N, Li X, Wu CW, Dong Y, Cai M, Mok MT, et al. Microrna-7 is a novel inhibitor of yy1 contributing to colorectal tumorigenesis. Oncogene. 2013;32:5078–88.CrossRefPubMed Zhang N, Li X, Wu CW, Dong Y, Cai M, Mok MT, et al. Microrna-7 is a novel inhibitor of yy1 contributing to colorectal tumorigenesis. Oncogene. 2013;32:5078–88.CrossRefPubMed
29.
go back to reference Kang W, Tong JH, Chan AW, Zhao J, Dong Y, Wang S, et al. Yin yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma. J Transl Med. 2014;12:80.CrossRefPubMedPubMedCentral Kang W, Tong JH, Chan AW, Zhao J, Dong Y, Wang S, et al. Yin yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma. J Transl Med. 2014;12:80.CrossRefPubMedPubMedCentral
30.
go back to reference Tang H, Wang Z, Liu Q, Liu X, Wu M, Li G. Disturbing mir-182 and −381 inhibits brd7 transcription and glioma growth by directly targeting lrrc4. PLoS One. 2014;9, e84146.CrossRefPubMedPubMedCentral Tang H, Wang Z, Liu Q, Liu X, Wu M, Li G. Disturbing mir-182 and −381 inhibits brd7 transcription and glioma growth by directly targeting lrrc4. PLoS One. 2014;9, e84146.CrossRefPubMedPubMedCentral
31.
go back to reference Liang HQ, Wang RJ, Diao CF, Li JW, Su JL, Zhang S. The pttg1-targeting mirnas mir-329, mir-300, mir-381, and mir-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/pttg1 regulation feedback loop. Oncotarget. 2015;6:29413–27.PubMedPubMedCentral Liang HQ, Wang RJ, Diao CF, Li JW, Su JL, Zhang S. The pttg1-targeting mirnas mir-329, mir-300, mir-381, and mir-655 inhibit pituitary tumor cell tumorigenesis and are involved in a p53/pttg1 regulation feedback loop. Oncotarget. 2015;6:29413–27.PubMedPubMedCentral
32.
go back to reference Vilming Elgaaen B, Olstad OK, Haug KB, Brusletto B, Sandvik L, Staff AC, et al. Global mirna expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed mirnas including mir-200c-3p as a prognostic marker. BMC Cancer. 2014;14:80.CrossRefPubMedPubMedCentral Vilming Elgaaen B, Olstad OK, Haug KB, Brusletto B, Sandvik L, Staff AC, et al. Global mirna expression analysis of serous and clear cell ovarian carcinomas identifies differentially expressed mirnas including mir-200c-3p as a prognostic marker. BMC Cancer. 2014;14:80.CrossRefPubMedPubMedCentral
33.
go back to reference Xia B, Yang S, Liu T, Lou G. Mir-211 suppresses epithelial ovarian cancer proliferation and cell-cycle progression by targeting cyclin d1 and cdk6. Mol Cancer. 2015;14:57.CrossRefPubMedPubMedCentral Xia B, Yang S, Liu T, Lou G. Mir-211 suppresses epithelial ovarian cancer proliferation and cell-cycle progression by targeting cyclin d1 and cdk6. Mol Cancer. 2015;14:57.CrossRefPubMedPubMedCentral
34.
go back to reference Wang CC, Chen JJ, Yang PC. Multifunctional transcription factor yy1: a therapeutic target in human cancer? Expert Opin Ther Targets. 2006;10:253–66.CrossRefPubMed Wang CC, Chen JJ, Yang PC. Multifunctional transcription factor yy1: a therapeutic target in human cancer? Expert Opin Ther Targets. 2006;10:253–66.CrossRefPubMed
35.
go back to reference Xu Y, Ohms SJ, Li Z, Wang Q, Gong G, Hu Y, et al. Changes in the expression of mir-381 and mir-495 are inversely associated with the expression of the mdr1 gene and development of multi-drug resistance. PLoS One. 2013;8, e82062.CrossRefPubMedPubMedCentral Xu Y, Ohms SJ, Li Z, Wang Q, Gong G, Hu Y, et al. Changes in the expression of mir-381 and mir-495 are inversely associated with the expression of the mdr1 gene and development of multi-drug resistance. PLoS One. 2013;8, e82062.CrossRefPubMedPubMedCentral
36.
go back to reference Ramos YF, Stad R, Attema J, Peltenburg LT, van der Eb AJ, Jochemsen AG. Aberrant expression of hdmx proteins in tumor cells correlates with wild-type p53. Cancer Res. 2001;61:1839–42.PubMed Ramos YF, Stad R, Attema J, Peltenburg LT, van der Eb AJ, Jochemsen AG. Aberrant expression of hdmx proteins in tumor cells correlates with wild-type p53. Cancer Res. 2001;61:1839–42.PubMed
37.
go back to reference Ryu SY, Kim K, Lee WS, Kwon HC, Lee KH, Kim CM, et al. Synergistic growth inhibition by combination of adenovirus mediated p53 transfer and cisplatin in ovarian cancer cell lines. J Gynecol Oncol. 2009;20:48–54.CrossRefPubMedPubMedCentral Ryu SY, Kim K, Lee WS, Kwon HC, Lee KH, Kim CM, et al. Synergistic growth inhibition by combination of adenovirus mediated p53 transfer and cisplatin in ovarian cancer cell lines. J Gynecol Oncol. 2009;20:48–54.CrossRefPubMedPubMedCentral
38.
go back to reference Liu Z, Gersbach E, Zhang X, Xu X, Dong R, Lee P, et al. Mir-106a represses the rb tumor suppressor p130 to regulate cellular proliferation and differentiation in high-grade serous ovarian carcinoma. Mol Cancer Res : MCR. 2013;11:1314–25.CrossRefPubMedPubMedCentral Liu Z, Gersbach E, Zhang X, Xu X, Dong R, Lee P, et al. Mir-106a represses the rb tumor suppressor p130 to regulate cellular proliferation and differentiation in high-grade serous ovarian carcinoma. Mol Cancer Res : MCR. 2013;11:1314–25.CrossRefPubMedPubMedCentral
39.
go back to reference Lee MH, Choi BY, Cho YY, Lee SY, Huang Z, Kundu JK, et al. Tumor suppressor p16(ink4a) inhibits cancer cell growth by downregulating eef1a2 through a direct interaction. J Cell Sci. 2013;126:1744–52.CrossRefPubMedPubMedCentral Lee MH, Choi BY, Cho YY, Lee SY, Huang Z, Kundu JK, et al. Tumor suppressor p16(ink4a) inhibits cancer cell growth by downregulating eef1a2 through a direct interaction. J Cell Sci. 2013;126:1744–52.CrossRefPubMedPubMedCentral
40.
go back to reference Huang L, Wang HY, Li JD, Wang JH, Zhou Y, Luo RZ, et al. Kpna2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-myc and downregulation of foxo3a. Cell Death Dis. 2013;4, e745.CrossRefPubMedPubMedCentral Huang L, Wang HY, Li JD, Wang JH, Zhou Y, Luo RZ, et al. Kpna2 promotes cell proliferation and tumorigenicity in epithelial ovarian carcinoma through upregulation of c-myc and downregulation of foxo3a. Cell Death Dis. 2013;4, e745.CrossRefPubMedPubMedCentral
41.
go back to reference Gan Y, Mo Y, Johnston J, Lu J, Wientjes MG, Au JL. Telomere maintenance in telomerase-positive human ovarian skov-3 cells cannot be retarded by complete inhibition of telomerase. FEBS Lett. 2002;527:10–4.CrossRefPubMed Gan Y, Mo Y, Johnston J, Lu J, Wientjes MG, Au JL. Telomere maintenance in telomerase-positive human ovarian skov-3 cells cannot be retarded by complete inhibition of telomerase. FEBS Lett. 2002;527:10–4.CrossRefPubMed
42.
go back to reference Oishi T, Kigawa J, Minagawa Y, Shimada M, Takahashi M, Terakawa N. Alteration of telomerase activity associated with development and extension of epithelial ovarian cancer. Obstet Gynecol. 1998;91:568–71.PubMed Oishi T, Kigawa J, Minagawa Y, Shimada M, Takahashi M, Terakawa N. Alteration of telomerase activity associated with development and extension of epithelial ovarian cancer. Obstet Gynecol. 1998;91:568–71.PubMed
43.
go back to reference Gatcliffe TA, Monk BJ, Planutis K, Holcombe RF. Wnt signaling in ovarian tumorigenesis. Int J Gynecol Cancer : Off J Int Gynecol Cancer Soc. 2008;18:954–62.CrossRef Gatcliffe TA, Monk BJ, Planutis K, Holcombe RF. Wnt signaling in ovarian tumorigenesis. Int J Gynecol Cancer : Off J Int Gynecol Cancer Soc. 2008;18:954–62.CrossRef
45.
go back to reference Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microrna target predictions. Nat Genet. 2005;37:495–500.CrossRefPubMed Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microrna target predictions. Nat Genet. 2005;37:495–500.CrossRefPubMed
Metadata
Title
MiR-381 inhibits epithelial ovarian cancer malignancy via YY1 suppression
Authors
Bairong Xia
Huiyan Li
Shanshan Yang
Tianbo Liu
Ge Lou
Publication date
01-07-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 7/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-4805-8

Other articles of this Issue 7/2016

Tumor Biology 7/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine