Skip to main content
Top
Published in: Journal of Experimental & Clinical Cancer Research 1/2013

Open Access 01-12-2013 | Research

The inhibitory role of Mir-29 in growth of breast cancer cells

Authors: Zhenglong Wu, Xiaona Huang, Xing Huang, Qiang Zou, Yujiang Guo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2013

Login to get access

Abstract

Mir-29 microRNA families are involved in regulation of various types of cancers. Although Mir-29 was shown to play an inhibitory role in tumorigenesis, the role of Mir-29 in breast cancer still remains obscure. In this study, we showed that Mir-29a is the dominant isoform in its family in mammary cells and expression of Mir-29a was down-regulated in different types of breast cancers. Furthermore, over-expression of Mir-29a resulted in significant slower growth of breast cancer cells and caused higher percentage of cells at G0/G1 phase. Consistent with this over-expression data, knockdown of Mir-29a in normal mammary cells lead to higher cell growth rate, and higher percentage of cells entering S phase. We further found that Mir-29a negatively regulated expression of B-Myb, which is a transcription factor associated with tumorigenesis. The protein levels of Cyclin A2 and D1 are consistent with the protein level of B-Myb. Taken together, our data suggests Mir-29a plays an important role in inhibiting growth of breast cancer cells and arresting cells at G0/G1 phase. Our data also suggests that Mir-29a may suppress tumor growth through down-regulating B-Myb.
Appendix
Available only for authorised users
Literature
1.
go back to reference Jemal A, et al: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59 (4): 225-249. 10.3322/caac.20006.CrossRef Jemal A, et al: Cancer statistics, 2009. CA Cancer J Clin. 2009, 59 (4): 225-249. 10.3322/caac.20006.CrossRef
2.
go back to reference Lin Y, et al: Striking life events associated with primary breast cancer susceptibility in women: a meta-analysis study. J Exp Clin Cancer Res. 2013, 32 (1): 53-10.1186/1756-9966-32-53.CrossRef Lin Y, et al: Striking life events associated with primary breast cancer susceptibility in women: a meta-analysis study. J Exp Clin Cancer Res. 2013, 32 (1): 53-10.1186/1756-9966-32-53.CrossRef
3.
go back to reference Iorio MV, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65 (16): 7065-7070. 10.1158/0008-5472.CAN-05-1783.CrossRef Iorio MV, et al: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65 (16): 7065-7070. 10.1158/0008-5472.CAN-05-1783.CrossRef
4.
go back to reference Wang C, et al: MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. J Exp Clin Cancer Res. 2012, 31: 58-10.1186/1756-9966-31-58.CrossRef Wang C, et al: MicroRNA-203 suppresses cell proliferation and migration by targeting BIRC5 and LASP1 in human triple-negative breast cancer cells. J Exp Clin Cancer Res. 2012, 31: 58-10.1186/1756-9966-31-58.CrossRef
5.
go back to reference Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 2009, 136 (2): 215-233. 10.1016/j.cell.2009.01.002.CrossRef Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 2009, 136 (2): 215-233. 10.1016/j.cell.2009.01.002.CrossRef
6.
go back to reference Chen F, Hu SJ: Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol. 2012, 26 (2): 79-86. 10.1002/jbt.20412.CrossRef Chen F, Hu SJ: Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol. 2012, 26 (2): 79-86. 10.1002/jbt.20412.CrossRef
7.
go back to reference He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004, 5 (7): 522-531. 10.1038/nrg1379.CrossRef He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004, 5 (7): 522-531. 10.1038/nrg1379.CrossRef
8.
go back to reference Plaisier CL, Pan M, Baliga NS: A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers. Genome Res. 2012, 22 (11): 2302-2314. 10.1101/gr.133991.111.CrossRef Plaisier CL, Pan M, Baliga NS: A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers. Genome Res. 2012, 22 (11): 2302-2314. 10.1101/gr.133991.111.CrossRef
9.
go back to reference Fan MQ, et al: Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma. J Exp Clin Cancer Res. 2013, 32 (1): 21-10.1186/1756-9966-32-21.CrossRef Fan MQ, et al: Decrease expression of microRNA-20a promotes cancer cell proliferation and predicts poor survival of hepatocellular carcinoma. J Exp Clin Cancer Res. 2013, 32 (1): 21-10.1186/1756-9966-32-21.CrossRef
10.
go back to reference Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6 (11): 857-866. 10.1038/nrc1997.CrossRef Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6 (11): 857-866. 10.1038/nrc1997.CrossRef
11.
go back to reference Creighton CJ, et al: Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma. PLoS One. 2012, 7 (3): e34546-10.1371/journal.pone.0034546.CrossRef Creighton CJ, et al: Integrated analyses of microRNAs demonstrate their widespread influence on gene expression in high-grade serous ovarian carcinoma. PLoS One. 2012, 7 (3): e34546-10.1371/journal.pone.0034546.CrossRef
12.
go back to reference Zhao JJ, et al: MicroRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 2010, 115 (13): 2630-2639. 10.1182/blood-2009-09-243147.CrossRef Zhao JJ, et al: MicroRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 2010, 115 (13): 2630-2639. 10.1182/blood-2009-09-243147.CrossRef
13.
go back to reference Garzon R, et al: MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009, 114 (26): 5331-5341. 10.1182/blood-2009-03-211938.CrossRef Garzon R, et al: MicroRNA 29b functions in acute myeloid leukemia. Blood. 2009, 114 (26): 5331-5341. 10.1182/blood-2009-03-211938.CrossRef
14.
go back to reference Ding Q, et al: APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. J Clin Invest. 2011, 121 (11): 4526-4536. 10.1172/JCI45008.CrossRef Ding Q, et al: APOBEC3G promotes liver metastasis in an orthotopic mouse model of colorectal cancer and predicts human hepatic metastasis. J Clin Invest. 2011, 121 (11): 4526-4536. 10.1172/JCI45008.CrossRef
15.
go back to reference Fabbri M, et al: MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007, 104 (40): 15805-15810. 10.1073/pnas.0707628104.CrossRef Fabbri M, et al: MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci USA. 2007, 104 (40): 15805-15810. 10.1073/pnas.0707628104.CrossRef
16.
go back to reference Cittelly DM, et al: Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4. Oncogene. 2012, 2 (20): 2555-2564. Cittelly DM, et al: Progestin suppression of miR-29 potentiates dedifferentiation of breast cancer cells via KLF4. Oncogene. 2012, 2 (20): 2555-2564.
17.
go back to reference Gebeshuber CA, Zatloukal K, Martinez J: miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. Embo Reports. 2009, 10 (4): 400-405. 10.1038/embor.2009.9.CrossRef Gebeshuber CA, Zatloukal K, Martinez J: miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. Embo Reports. 2009, 10 (4): 400-405. 10.1038/embor.2009.9.CrossRef
18.
go back to reference Xiong Y, et al: Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010, 51 (3): 836-845. Xiong Y, et al: Effects of microRNA-29 on apoptosis, tumorigenicity, and prognosis of hepatocellular carcinoma. Hepatology. 2010, 51 (3): 836-845.
19.
go back to reference Calin GA, et al: A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005, 353 (17): 1793-1801. 10.1056/NEJMoa050995.CrossRef Calin GA, et al: A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005, 353 (17): 1793-1801. 10.1056/NEJMoa050995.CrossRef
20.
go back to reference Mott JL, et al: mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007, 26 (42): 6133-6140. 10.1038/sj.onc.1210436.CrossRef Mott JL, et al: mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007, 26 (42): 6133-6140. 10.1038/sj.onc.1210436.CrossRef
21.
go back to reference Yanaihara N, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9 (3): 189-198. 10.1016/j.ccr.2006.01.025.CrossRef Yanaihara N, et al: Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006, 9 (3): 189-198. 10.1016/j.ccr.2006.01.025.CrossRef
22.
go back to reference Martinez I, et al: miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc Natl Acad Sci U S A. 2011, 108 (2): 522-527. 10.1073/pnas.1017346108.CrossRef Martinez I, et al: miR-29 and miR-30 regulate B-Myb expression during cellular senescence. Proc Natl Acad Sci U S A. 2011, 108 (2): 522-527. 10.1073/pnas.1017346108.CrossRef
23.
go back to reference Muniyappa MK, et al: MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. Eur J Cancer. 2009, 45 (17): 3104-3118. 10.1016/j.ejca.2009.09.014.CrossRef Muniyappa MK, et al: MiRNA-29a regulates the expression of numerous proteins and reduces the invasiveness and proliferation of human carcinoma cell lines. Eur J Cancer. 2009, 45 (17): 3104-3118. 10.1016/j.ejca.2009.09.014.CrossRef
24.
go back to reference Xu H, et al: MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res. 2009, 69 (15): 6275-6281. 10.1158/0008-5472.CAN-08-4517.CrossRef Xu H, et al: MicroRNA miR-29 modulates expression of immunoinhibitory molecule B7-H3: potential implications for immune based therapy of human solid tumors. Cancer Res. 2009, 69 (15): 6275-6281. 10.1158/0008-5472.CAN-08-4517.CrossRef
25.
go back to reference Santanam U, et al: Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A. 2010, 107 (27): 12210-12215. 10.1073/pnas.1007186107.CrossRef Santanam U, et al: Chronic lymphocytic leukemia modeled in mouse by targeted miR-29 expression. Proc Natl Acad Sci U S A. 2010, 107 (27): 12210-12215. 10.1073/pnas.1007186107.CrossRef
26.
go back to reference Cui Y, et al: MiR-29a inhibits cell proliferation and induces cell cycle arrest through the downregulation of p42.3 In human gastric cancer. Plos One. 2011, 6 (10): e25872-10.1371/journal.pone.0025872.CrossRef Cui Y, et al: MiR-29a inhibits cell proliferation and induces cell cycle arrest through the downregulation of p42.3 In human gastric cancer. Plos One. 2011, 6 (10): e25872-10.1371/journal.pone.0025872.CrossRef
27.
go back to reference Sala A: B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer. Eur J Cancer. 2005, 41 (16): 2479-2484. 10.1016/j.ejca.2005.08.004.CrossRef Sala A: B-MYB, a transcription factor implicated in regulating cell cycle, apoptosis and cancer. Eur J Cancer. 2005, 41 (16): 2479-2484. 10.1016/j.ejca.2005.08.004.CrossRef
28.
go back to reference Roy PG, Thompson AM: Cyclin D1 and breast cancer. Breast. 2006, 15 (6): 718-727. 10.1016/j.breast.2006.02.005.CrossRef Roy PG, Thompson AM: Cyclin D1 and breast cancer. Breast. 2006, 15 (6): 718-727. 10.1016/j.breast.2006.02.005.CrossRef
29.
go back to reference Huuhtanen RL, et al: Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness. Cancer Res. 1999, 59 (12): 2885-2890. Huuhtanen RL, et al: Expression of cyclin A in soft tissue sarcomas correlates with tumor aggressiveness. Cancer Res. 1999, 59 (12): 2885-2890.
30.
go back to reference Poikonen P, et al: Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer. Br J Cancer. 2005, 93 (5): 515-519. 10.1038/sj.bjc.6602735.CrossRef Poikonen P, et al: Cyclin A as a marker for prognosis and chemotherapy response in advanced breast cancer. Br J Cancer. 2005, 93 (5): 515-519. 10.1038/sj.bjc.6602735.CrossRef
31.
go back to reference Wang X, et al: Knocking-down cyclin A(2) by siRNA suppresses apoptosis and switches differentiation pathways in K562 cells upon administration with doxorubicin. PLoS One. 2009, 4 (8): e6665-10.1371/journal.pone.0006665.CrossRef Wang X, et al: Knocking-down cyclin A(2) by siRNA suppresses apoptosis and switches differentiation pathways in K562 cells upon administration with doxorubicin. PLoS One. 2009, 4 (8): e6665-10.1371/journal.pone.0006665.CrossRef
Metadata
Title
The inhibitory role of Mir-29 in growth of breast cancer cells
Authors
Zhenglong Wu
Xiaona Huang
Xing Huang
Qiang Zou
Yujiang Guo
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2013
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-32-98

Other articles of this Issue 1/2013

Journal of Experimental & Clinical Cancer Research 1/2013 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