Skip to main content
Top
Published in: Tumor Biology 12/2015

01-12-2015 | Research Article

miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer

Authors: Haifeng Wang, Wei Zhang, Yigang Zuo, Mingxia Ding, Changxing Ke, Ruping Yan, Hui Zhan, Jingyu Liu, Jiansong Wang

Published in: Tumor Biology | Issue 12/2015

Login to get access

Abstract

MicroRNA-9 upregulation was reported in several tumors. However, its function and mechanism in human bladder cancer remains obscure. The present study aims to identify the expression pattern, biological roles and potential mechanism of miR-9 in human bladder cancers. We found that expression level of miR-9 in bladder cancer tissues was higher than normal tissues. miR-9 mimic transfection was performed in T24 and 5637 cells with low miR-9 expression, and miR-9 inhibitor was employed in BIU-87 cell line with high endogenous expression. miR-9 increased cell proliferation, cell cycle progression, invasion and chemoresistance, with upregulation of cyclin D1, MMP9, Bcl-2, and survivin and downregulation of E-cadherin. Using luciferase reporter assay, we confirmed that LASS2 was a direct target of miR-9 in bladder cancer cells. Transfection of miR-9 mimic downregulated LASS2 expression. LASS2 transfection downregulated Bcl-2 and survivin expression, which were induced by miR-9 mimic in both cell lines. In conclusion, these results indicate that miR-9 upregulation might be associated with malignant phenotype of bladder cancer. miR-9 promotes chemoresistance of bladder cancer cells by target LASS2.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dinney CP, McConkey DJ, Millikan RE, Wu X, Bar-Eli M, Adam L, et al. Focus on bladder cancer. Cancer Cell. 2004;6(2):111–6.CrossRefPubMed Dinney CP, McConkey DJ, Millikan RE, Wu X, Bar-Eli M, Adam L, et al. Focus on bladder cancer. Cancer Cell. 2004;6(2):111–6.CrossRefPubMed
3.
go back to reference Hobert O. Gene regulation by transcription factors and microRNAs. Science. 2008;319(5871):1785–6.CrossRefPubMed Hobert O. Gene regulation by transcription factors and microRNAs. Science. 2008;319(5871):1785–6.CrossRefPubMed
5.
go back to reference Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102–14.CrossRefPubMed Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9(2):102–14.CrossRefPubMed
6.
go back to reference Lv S, Turlova E, Zhao S, Kang H, Han M, Sun HS. Prognostic and clinicopathological significance of survivin expression in bladder cancer patients: a meta-analysis. Tumour Biol. 2014;35(2):1565–74.CrossRefPubMed Lv S, Turlova E, Zhao S, Kang H, Han M, Sun HS. Prognostic and clinicopathological significance of survivin expression in bladder cancer patients: a meta-analysis. Tumour Biol. 2014;35(2):1565–74.CrossRefPubMed
7.
go back to reference Ostenfeld MS, Bramsen JB, Lamy P, Villadsen SB, Fristrup N, Sorensen KD, et al. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors. Oncogene. 2010;29(7):1073–84.CrossRefPubMed Ostenfeld MS, Bramsen JB, Lamy P, Villadsen SB, Fristrup N, Sorensen KD, et al. miR-145 induces caspase-dependent and -independent cell death in urothelial cancer cell lines with targeting of an expression signature present in Ta bladder tumors. Oncogene. 2010;29(7):1073–84.CrossRefPubMed
8.
go back to reference Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, et al. microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer. 2013;132(11):2479–91.CrossRefPubMed Pignot G, Cizeron-Clairac G, Vacher S, Susini A, Tozlu S, Vieillefond A, et al. microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int J Cancer. 2013;132(11):2479–91.CrossRefPubMed
9.
go back to reference Gwak JM, Kim HJ, Kim EJ, Chung YR, Yun S, Seo AN, et al. MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer. Breast Cancer Res Treat. 2014;147(1):39–49.CrossRefPubMed Gwak JM, Kim HJ, Kim EJ, Chung YR, Yun S, Seo AN, et al. MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer. Breast Cancer Res Treat. 2014;147(1):39–49.CrossRefPubMed
10.
go back to reference Xing F, Sharma S, Liu Y, Mo YY, Wu K, Zhang YY, et al., miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-alpha. Oncogene, 2015. Xing F, Sharma S, Liu Y, Mo YY, Wu K, Zhang YY, et al., miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF-alpha. Oncogene, 2015.
11.
go back to reference Chen P, Price C, Li Z, Li Y, Cao D, Wiley A, et al. miR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia-rearranged leukemia. Proc Natl Acad Sci USA. 2013;110(28):11511–6.CrossRefPubMedPubMedCentral Chen P, Price C, Li Z, Li Y, Cao D, Wiley A, et al. miR-9 is an essential oncogenic microRNA specifically overexpressed in mixed lineage leukemia-rearranged leukemia. Proc Natl Acad Sci USA. 2013;110(28):11511–6.CrossRefPubMedPubMedCentral
12.
go back to reference Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A, et al. MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol. 2009;19(3):375–83.CrossRefPubMedPubMedCentral Nass D, Rosenwald S, Meiri E, Gilad S, Tabibian-Keissar H, Schlosberg A, et al. MiR-92b and miR-9/9* are specifically expressed in brain primary tumors and can be used to differentiate primary from metastatic brain tumors. Brain Pathol. 2009;19(3):375–83.CrossRefPubMedPubMedCentral
13.
go back to reference Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.CrossRefPubMed Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.CrossRefPubMed
14.
go back to reference Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, et al. Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat. 2009;118(1):185–96.CrossRefPubMed Sun Y, Wu J, Wu SH, Thakur A, Bollig A, Huang Y, et al. Expression profile of microRNAs in c-Myc induced mouse mammary tumors. Breast Cancer Res Treat. 2009;118(1):185–96.CrossRefPubMed
15.
go back to reference Cai L, Cai X. Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma. Diagn Pathol. 2014;9(1):1000.CrossRefPubMedPubMedCentral Cai L, Cai X. Up-regulation of miR-9 expression predicate advanced clinicopathological features and poor prognosis in patients with hepatocellular carcinoma. Diagn Pathol. 2014;9(1):1000.CrossRefPubMedPubMedCentral
16.
go back to reference Xu T, Liu X, Han L, Shen H, Liu L, Shu Y. Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer. Clin Transl Oncol. 2014;16(5):469–75.CrossRefPubMed Xu T, Liu X, Han L, Shen H, Liu L, Shu Y. Up-regulation of miR-9 expression as a poor prognostic biomarker in patients with non-small cell lung cancer. Clin Transl Oncol. 2014;16(5):469–75.CrossRefPubMed
17.
go back to reference Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247–56.PubMedPubMedCentral Ma L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, et al. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol. 2010;12(3):247–56.PubMedPubMedCentral
18.
go back to reference White RA, Neiman JM, Reddi A, Han G, Birlea S, Mitra D, et al. Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest. 2013;123(10):4390–404.CrossRefPubMedPubMedCentral White RA, Neiman JM, Reddi A, Han G, Birlea S, Mitra D, et al. Epithelial stem cell mutations that promote squamous cell carcinoma metastasis. J Clin Invest. 2013;123(10):4390–404.CrossRefPubMedPubMedCentral
19.
go back to reference Sun C, Li N, Yang Z, Zhou B, He Y, Weng D, et al. miR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition. J Natl Cancer Inst. 2013;105(22):1750–8.CrossRefPubMed Sun C, Li N, Yang Z, Zhou B, He Y, Weng D, et al. miR-9 regulation of BRCA1 and ovarian cancer sensitivity to cisplatin and PARP inhibition. J Natl Cancer Inst. 2013;105(22):1750–8.CrossRefPubMed
20.
go back to reference Song Y, Li J, Zhu Y, Dai Y, Zeng T, Liu L, et al. MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal squamous cell carcinoma. Oncotarget. 2014;5(22):11669–80.CrossRefPubMedPubMedCentral Song Y, Li J, Zhu Y, Dai Y, Zeng T, Liu L, et al. MicroRNA-9 promotes tumor metastasis via repressing E-cadherin in esophageal squamous cell carcinoma. Oncotarget. 2014;5(22):11669–80.CrossRefPubMedPubMedCentral
21.
go back to reference Kumar B, Koul S, Petersen J, Khandrika L, Hwa JS, Meacham RB, et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res. 2010;70(2):832–41.CrossRefPubMed Kumar B, Koul S, Petersen J, Khandrika L, Hwa JS, Meacham RB, et al. p38 mitogen-activated protein kinase-driven MAPKAPK2 regulates invasion of bladder cancer by modulation of MMP-2 and MMP-9 activity. Cancer Res. 2010;70(2):832–41.CrossRefPubMed
22.
go back to reference Rebel JM, Thijssen CD, Vermey M, Delouvee A, Zwarthoff EC, Van der Kwast TH. E-cadherin expression determines the mode of replacement of normal urothelium by human bladder carcinoma cells. Cancer Res. 1994;54(20):5488–92.PubMed Rebel JM, Thijssen CD, Vermey M, Delouvee A, Zwarthoff EC, Van der Kwast TH. E-cadherin expression determines the mode of replacement of normal urothelium by human bladder carcinoma cells. Cancer Res. 1994;54(20):5488–92.PubMed
23.
go back to reference Miyake H, Hara S, Arakawa S, Kamidono S, Hara I. Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo. Int J Cancer. 2001;93(1):26–32.CrossRefPubMed Miyake H, Hara S, Arakawa S, Kamidono S, Hara I. Overexpression of Bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells both in vitro and in vivo. Int J Cancer. 2001;93(1):26–32.CrossRefPubMed
24.
go back to reference Miyake H, Hara I, Yamanaka K, Arakawa S, Kamidono S. Synergistic enhancement of resistance to cisplatin in human bladder cancer cells by overexpression of mutant-type p53 and Bcl-2. J Urol. 1999;162(6):2176–81.CrossRefPubMed Miyake H, Hara I, Yamanaka K, Arakawa S, Kamidono S. Synergistic enhancement of resistance to cisplatin in human bladder cancer cells by overexpression of mutant-type p53 and Bcl-2. J Urol. 1999;162(6):2176–81.CrossRefPubMed
25.
go back to reference Jeon C, Kim M, Kwak C, Kim HH, Ku JH. Prognostic role of survivin in bladder cancer: a systematic review and meta-analysis. PLoS One. 2013;8(10), e76719.CrossRefPubMedPubMedCentral Jeon C, Kim M, Kwak C, Kim HH, Ku JH. Prognostic role of survivin in bladder cancer: a systematic review and meta-analysis. PLoS One. 2013;8(10), e76719.CrossRefPubMedPubMedCentral
26.
go back to reference Mei F, You J, Liu B, Zhang M, Liu J, Zhang B, et al., LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity. Tumour Biol. 2014. Mei F, You J, Liu B, Zhang M, Liu J, Zhang B, et al., LASS2/TMSG1 inhibits growth and invasion of breast cancer cell in vitro through regulation of vacuolar ATPase activity. Tumour Biol. 2014.
27.
go back to reference Xu X, Liu B, Zou P, Zhang Y, You J, Pei F. Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell. J Cell Biochem. 2014;115(4):731–43.CrossRefPubMed Xu X, Liu B, Zou P, Zhang Y, You J, Pei F. Silencing of LASS2/TMSG1 enhances invasion and metastasis capacity of prostate cancer cell. J Cell Biochem. 2014;115(4):731–43.CrossRefPubMed
28.
go back to reference Chen L, Lu X, Zeng T, Chen Y, Chen Q, Wu W, et al. Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncol Rep. 2014;31(2):885–93.PubMed Chen L, Lu X, Zeng T, Chen Y, Chen Q, Wu W, et al. Enhancement of DEN-induced liver tumourigenesis in hepatocyte-specific Lass2-knockout mice coincident with upregulation of the TGF-β1-Smad4-PAI-1 axis. Oncol Rep. 2014;31(2):885–93.PubMed
29.
go back to reference Wang H, Wang J, Zuo Y, Ding M, Yan R, Yang D, et al. Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med Oncol. 2012;29(3):1921–7.CrossRefPubMed Wang H, Wang J, Zuo Y, Ding M, Yan R, Yang D, et al. Expression and prognostic significance of a new tumor metastasis suppressor gene LASS2 in human bladder carcinoma. Med Oncol. 2012;29(3):1921–7.CrossRefPubMed
30.
go back to reference Zhao Q, Wang H, Yang M, Yang D, Zuo Y, Wang J. Expression of a tumor-associated gene, LASS2, in the human bladder carcinoma cell lines BIU-87, T24, EJ and EJ-M3. Exp Ther Med. 2013;5(3):942–6.PubMedPubMedCentral Zhao Q, Wang H, Yang M, Yang D, Zuo Y, Wang J. Expression of a tumor-associated gene, LASS2, in the human bladder carcinoma cell lines BIU-87, T24, EJ and EJ-M3. Exp Ther Med. 2013;5(3):942–6.PubMedPubMedCentral
Metadata
Title
miR-9 promotes cell proliferation and inhibits apoptosis by targeting LASS2 in bladder cancer
Authors
Haifeng Wang
Wei Zhang
Yigang Zuo
Mingxia Ding
Changxing Ke
Ruping Yan
Hui Zhan
Jingyu Liu
Jiansong Wang
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 12/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3713-7

Other articles of this Issue 12/2015

Tumor Biology 12/2015 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