microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

Qin,Xiaoyan; Yan,Lei; Zhao,Xingbo; Li,Chunyan; Fu,Yibing

doi:10.3892/ol.2012.896

December 2012 Volume 4 Issue 6

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

December 2012 Volume 4 Issue 6

Full Size Image

Article

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

Authors:
- Xiaoyan Qin
- Lei Yan
- Xingbo Zhao
- Chunyan Li
- Yibing Fu
View Affiliations / Copyright

Affiliations: Department of Obstetrics and Gynaecology, Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China
Pages: 1290-1296
|
Published online on: September 6, 2012

https://doi.org/10.3892/ol.2012.896
Expand metrics +

Abstract

The aim of this study was to investigate the role of microRNA-21 (miR-21) in the regulation of phosphatase and tensin homolog deleted from chromosome-10 (PTEN) expression and proliferation of endometrioid endometrial cancer (EEC) cells. We performed a qRT-PCR assay with miR-21 and PTEN in 16 paired EEC tumor tissues and adjacent non-tumor endometrium. To investigate the regulation of PTEN by miR-21, we designed gain- and loss-of-function of miR-21 experiments in the KLE cell line by transfection with a synthetic miR-21 mimic and inhibitor. To validate the putative binding site of miR-21 in the 3' untranslated region (3'-UTR) of PTEN messenger RNA (mRNA), a dual-luciferase reporter assay was carried out. To evaluate the potential effect of miR-21 on EEC proliferation, we performed both overexpression experiments, using an miR-21 mimic, and inhibition assays, using an miR-21 inhibitor. miR-21 was overexpressed in EEC and was inversely correlated with PTEN protein expression (P<0.001). miR-21 regulated PTEN protein expression and cell proliferation in the KLE cell line and the direct binding of miR-21 to the PTEN 3'-UTR was confirmed using a dual-luciferase reporter assay. The upregulation of miR-21 led to a significant decrease in the PTEN protein expression level (P=0.007). The downregulation of miR-21 led to a significant increase in PTEN protein (P=0.002). The expression of luciferase in the wt-PTEN-3'-UTR-pGL3 group was downregulated in the presence of the miR-21 mimic (P=0.001). miR-21 was overexpressed in EEC. In conclusion, we demonstrated that the expression of PTEN protein, but not mRNA, was negatively directly regulated by miR-21 in the KLE cell line. The overexpression of miR-21 modulated EEC cell proliferation through the downregulation of PTEN.

View Figures

View References

1.	A JemalR SiegelE WardJ XuCancer statistics, 2010CA Cancer J Clin60277300201010.3322/caac.20073
2.	H TashiroMS BlazesR WuMutations in PTEN are frequent in endometrial carcinoma but rare in other common gynecological malignanciesCancer Res573935394019979307275
3.	A PerrenLP WengAH BoagImmunohistochemical evidence of loss of PTEN expression in primary ductal adenocarcinomas of the breastAm J Pathol15512531260199910.1016/S0002-9440(10)65227-310514407
4.	DP BartelMicroRNAs: genomics, biogenesis, mechanism, and functionCell116281297200410.1016/S0092-8674(04)00045-514744438
5.	YS LeeA DuttaMicroRNAs in cancerAnnu Rev Pathol4199227200910.1146/annurev.pathol.4.110807.092222
6.	F MengR HensonM LangInvolvement of human micro-RNA in growth and response to chemotherapy in human cholangiocarcinoma cell linesGastroenterology13021132129200610.1053/j.gastro.2006.02.05716762633
7.	F MengR HensonH Wehbe-JanekMicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancerGastroenterology133647658200710.1053/j.gastro.2007.05.02217681183
8.	IA AsanganiSA RasheedDA NikolovaMicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancerOncogene2721282136200810.1038/sj.onc.1210856
9.	LB FrankelNR ChristoffersenA JacobsenProgrammed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cellsJ Biol Chem28310261033200810.1074/jbc.M70722420017991735
10.	S ZhuH WuF WuMicroRNA-21 targets tumor suppressor genes in invasion and metastasisCell Res18350359200810.1038/cr.2008.2418270520
11.	Q YaoH XuQQ ZhangMicroRNA-21 promotes cell proliferation and down-regulates the expression of programmed cell death 4 (PDCD4) in HeLa cervical carcinoma cellsBiochem Biophys Res Commun388539542200910.1016/j.bbrc.2009.08.04419682430
12.	ML SiS ZhuH WumiR-21-mediated tumor growthOncogene2627992803200710.1038/sj.onc.121008317072344
13.	S ZhuML SiH WuYY MoMicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1)J Biol Chem2821432814336200710.1074/jbc.M61139320017363372
14.	W QinB ZhaoY ShiBMPRII is a direct target of miR-21Acta Biochim Biophys Sin (Shanghai)41618623200910.1093/abbs/gmp04919578724
15.	D SayedS RaneJ LypowyMicroRNA-21 targets Sprouty2 and promotes cellular outgrowthsMol Biol Cell1932723282200810.1091/mbc.E08-02-015918508928
16.	A TorresK TorresT PaszkowskiHighly increased maspin expression corresponds with up-regulation of miR-21 in endometrial cancer: a preliminary reportInt J Gynecol Cancer21814201110.1097/IGC.0b013e318200050e21330826
17.	J SnowdonX ZhangT ChildsThe microRNA-200 family is upregulated in endometrial carcinomaPLoS One6e22828201110.1371/journal.pone.002282821897839
18.	LA RamónA Braza-BoïlsJ Gilabert-EstellésmicroRNAs expression in endometriosis and their relation to angiogenic factorsHum Reprod2610821090201121335415
19.	Q PanX LuoN CheginimicroRNA 21: response to hormonal therapies and regulatory function in leiomyoma, transformed leiomyoma and leiomyosarcoma cellsMol Hum Reprod16215227201010.1093/molehr/gap093
20.	DE CohnM FabbriN ValeriComprehensive miRNA profiling of surgically staged endometrial cancerAm J Obstet Gynecol202656 e18201020400061
21.	EJ LeeY GusevJ JiangExpression profiling identifies microRNA signature in pancreatic cancerInt J Cancer12010461054200710.1002/ijc.2239417149698
22.	S VoliniaGA CalinCG LiuA microRNA expression signature of human solid tumors defines cancer gene targetsProc Natl Acad Sci USA10322572261200610.1073/pnas.051056510316461460
23.	WJ MaGD LvA TuersunRole of microRNA-21 and effect on PTEN in Kazakh’s esophageal squamous cell carcinomaMol Biol Rep3832533260201121104017
24.	PK VogtM GymnopoulosJR HartPI 3-kinase and cancer: changing accentsCurr Opin Genet Dev191217200910.1016/j.gde.2008.11.01119185485
25.	KH SeoHS LeeB JungEstrogen enhances angiogenesis through a pathway involving platelet-activating factor-mediated nuclear factor-kappaB activationCancer Res6464826488200410.1158/0008-5472.CAN-03-2774

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

microRNA-21 overexpression contributes to cell proliferation by targeting PTEN in endometrioid endometrial cancer

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Related Articles