Skip to main content
Top
Published in: Medical Oncology 1/2013

01-03-2013 | Original Paper

miR-130b is an EMT-related microRNA that targets DICER1 for aggression in endometrial cancer

Authors: Bi-Lan Li, Cong Lu, Wen Lu, Ting-ting Yang, Junjie Qu, Xiayu Hong, Xiao-ping Wan

Published in: Medical Oncology | Issue 1/2013

Login to get access

Abstract

Endometrial cancer (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. Certain microRNAs (miRNAs) and DICER1 play important roles in cell motility and survival. This study investigated the role of miR-130b and DICER1 in EC. We profiled miR-130b and DICER1 expression in clinical samples explored its relationship with clinical parameters. A luciferase reporter assay assessed the miR-130b targeting potential of DICER1. We show both in vitro and in vivo that miR-130b overexpression along with DICER1 dysfunction leads to tumor aggression and miRNA synthesis abnormalities that are related to cancer hallmarks through DICER1–miRNAs axis modulation. We also identify the mechanism related to this potential tumor predisposing phenotype: miR-130b and loss of DICER1 induced abnormal expression of EMT-related genes, which constitutes a loop regulation of the miR-130b–DICER1–EMT axis.
Literature
1.
go back to reference Azueta A, Gatius S, Matias-Guiu X. Endometrioid carcinoma of the endometrium: pathologic and molecular features. Semin Diagn Pathol. 2010;27:226–40.PubMedCrossRef Azueta A, Gatius S, Matias-Guiu X. Endometrioid carcinoma of the endometrium: pathologic and molecular features. Semin Diagn Pathol. 2010;27:226–40.PubMedCrossRef
2.
go back to reference Dedes KJ, Wetterskog D, Ashworth A, Kaye SB, Reis-Filho JS. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011;8:261–71.PubMedCrossRef Dedes KJ, Wetterskog D, Ashworth A, Kaye SB, Reis-Filho JS. Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011;8:261–71.PubMedCrossRef
3.
go back to reference Chaudhry P, Asselin E. Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr Relat Cancer. 2009;16:363–80.PubMedCrossRef Chaudhry P, Asselin E. Resistance to chemotherapy and hormone therapy in endometrial cancer. Endocr Relat Cancer. 2009;16:363–80.PubMedCrossRef
4.
go back to reference Hammond SM. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett. 2005;579:5822–9.PubMedCrossRef Hammond SM. Dicing and slicing: the core machinery of the RNA interference pathway. FEBS Lett. 2005;579:5822–9.PubMedCrossRef
5.
go back to reference Karube Y, Tanaka H, Osada H, et al. Reduced expression of DICER1 associated with poor prognosis in lung cancer patients. Cancer Sci. 2005;96:111–5.PubMedCrossRef Karube Y, Tanaka H, Osada H, et al. Reduced expression of DICER1 associated with poor prognosis in lung cancer patients. Cancer Sci. 2005;96:111–5.PubMedCrossRef
6.
7.
go back to reference Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T. Dicer1 functions as a haploinsufficient tumosuppressor. Genes Dev. 2009;23:2700–4.PubMedCrossRef Kumar MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T. Dicer1 functions as a haploinsufficient tumosuppressor. Genes Dev. 2009;23:2700–4.PubMedCrossRef
8.
9.
go back to reference Yang C, Cai J, Wang Q, Tang H, Cao J, Liying W, Wang Z. Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1. Gynecol Oncol. 2012;124:325–34.PubMedCrossRef Yang C, Cai J, Wang Q, Tang H, Cao J, Liying W, Wang Z. Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1. Gynecol Oncol. 2012;124:325–34.PubMedCrossRef
10.
go back to reference Abu-Rustum NR, Zhou Q, Iasonos A, Alektiar KM, et al. The revised 2009 FIGO staging system for endometrial cancer: should the 1988 FIGO stages IA and IB be altered? Int J Gynecol Cancer. 2010;21:511–6.CrossRef Abu-Rustum NR, Zhou Q, Iasonos A, Alektiar KM, et al. The revised 2009 FIGO staging system for endometrial cancer: should the 1988 FIGO stages IA and IB be altered? Int J Gynecol Cancer. 2010;21:511–6.CrossRef
11.
go back to reference Gregory PA, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting zeb1 and sip1. Nat Cell Biol. 2008;10:593–601.PubMedCrossRef Gregory PA, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting zeb1 and sip1. Nat Cell Biol. 2008;10:593–601.PubMedCrossRef
12.
go back to reference Kim BH, Hong SW, Kim A, Choi SH, Yoon SO. Prognostic implications for high expression of oncogenic microRNAs in advanced gastric carcinoma. J Surg Oncol. 2012. doi:10.1002/jso.23271. Kim BH, Hong SW, Kim A, Choi SH, Yoon SO. Prognostic implications for high expression of oncogenic microRNAs in advanced gastric carcinoma. J Surg Oncol. 2012. doi:10.​1002/​jso.​23271.
13.
go back to reference Ferraz C, Lorenz S, Wojtas B, Bornstein SR, Paschke R, Eszlinger M. Inverse correlation of miRNA and cell cycle-associated genes suggests influence of miRNA on benign thyroid nodule tumorigenesis. J Clin Endocrinol Metab. 2013; 98(1):E8–E16. Ferraz C, Lorenz S, Wojtas B, Bornstein SR, Paschke R, Eszlinger M. Inverse correlation of miRNA and cell cycle-associated genes suggests influence of miRNA on benign thyroid nodule tumorigenesis. J Clin Endocrinol Metab. 2013; 98(1):E8–E16.
14.
go back to reference Lai KW, Koh KX, Loh M. MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer. 2010;46:1456–63.PubMedCrossRef Lai KW, Koh KX, Loh M. MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer. 2010;46:1456–63.PubMedCrossRef
15.
go back to reference Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39(5):673–7.PubMedCrossRef Kumar MS, Lu J, Mercer KL, Golub TR, Jacks T. Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 2007;39(5):673–7.PubMedCrossRef
16.
go back to reference Karube Y, Tanaka H, Osada H. Reduced expression of DICER1 associated with poor prognosis in lung cancer patients. Cancer Sci. 2005;96:111–5.PubMedCrossRef Karube Y, Tanaka H, Osada H. Reduced expression of DICER1 associated with poor prognosis in lung cancer patients. Cancer Sci. 2005;96:111–5.PubMedCrossRef
17.
go back to reference Kawase-Koga Y, Low R, Otaegi G, Pollock A, et al. RNAase-III enzyme DICER1 maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells. J Cell Sci. 2010;123:586–94.PubMedCrossRef Kawase-Koga Y, Low R, Otaegi G, Pollock A, et al. RNAase-III enzyme DICER1 maintains signaling pathways for differentiation and survival in mouse cortical neural stem cells. J Cell Sci. 2010;123:586–94.PubMedCrossRef
18.
go back to reference Zhang L, et al. DICER1 ablation impairs prostate stem cell activity and causes prostate atrophy. Stem Cells. 2010;28(7):1260–9.PubMed Zhang L, et al. DICER1 ablation impairs prostate stem cell activity and causes prostate atrophy. Stem Cells. 2010;28(7):1260–9.PubMed
19.
go back to reference Suárez Y, Fernandez-Hernando C, Pober JS, Sessa WC. DICER1 dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007;100:1164–73.PubMedCrossRef Suárez Y, Fernandez-Hernando C, Pober JS, Sessa WC. DICER1 dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res. 2007;100:1164–73.PubMedCrossRef
20.
go back to reference Aglund K, Rauvala M, Puistola U, Angstrom T, TurpeenniemiHujanen T, Zackrisson B, Stendahl U. Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage. Gynecol Oncol. 2004;94:699–704.PubMedCrossRef Aglund K, Rauvala M, Puistola U, Angstrom T, TurpeenniemiHujanen T, Zackrisson B, Stendahl U. Gelatinases A and B (MMP-2 and MMP-9) in endometrial cancer-MMP-9 correlates to the grade and the stage. Gynecol Oncol. 2004;94:699–704.PubMedCrossRef
21.
go back to reference Filipowicz W, Bhattacharyya SN, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008;9:102–114. Filipowicz W, Bhattacharyya SN, Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 2008;9:102–114.
Metadata
Title
miR-130b is an EMT-related microRNA that targets DICER1 for aggression in endometrial cancer
Authors
Bi-Lan Li
Cong Lu
Wen Lu
Ting-ting Yang
Junjie Qu
Xiayu Hong
Xiao-ping Wan
Publication date
01-03-2013
Publisher
Springer US
Published in
Medical Oncology / Issue 1/2013
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0484-0

Other articles of this Issue 1/2013

Medical Oncology 1/2013 Go to the issue