MicroRNA-20a Overexpression Inhibited Proliferation and Metastasis of Pancreatic Carcinoma Cells

被引：56

作者：

Yan, Haijiao ^{[1
]}

Wu, Jiangxue ^{[1
]}

Liu, Wensong ^{[3
]}

Zuo, Yufang ^{[1
]}

Chen, Shupeng ^{[1
]}

Zhang, Shineng ^{[4
]}

Zeng, Musheng ^{[1
]}

Huang, Wenlin ^{[1
,2
]}

机构：

[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol S China, Guangzhou 510060, Guangdong, Peoples R China

[2] Chinese Acad Sci, Inst Microbiol, Beijing 100080, Peoples R China

[3] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Gen Surg, Wuxi 214023, Jiangsu, Peoples R China

[4] Sun Yat Sen Univ, Affiliated Hosp 2, Dept Gastroenterol, Guangzhou 510120, Guangdong, Peoples R China

来源：

HUMAN GENE THERAPY | 2010年 / 21卷 / 12期

基金：

国家高技术研究发展计划(863计划);

关键词：

IN-SITU DETECTION; CANCER-CELLS; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; CHROMOSOME; 13Q; GROWTH-FACTOR; EXPRESSION; INVASION; STAT3; ACTIVATION;

D O I：

10.1089/hum.2010.061

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

The aim of this study was to investigate the effect of microRNA-20a on pancreatic carcinoma cell proliferation and invasion and to find a new effective treatment strategy for pancreatic carcinoma. MicroRNA-20a expression was determined in 10 matched normal pancreatic tissues and pancreatic carcinoma by in situ hybridization. Quantitative real-time RT-PCR was used to evaluate the expression of microRNA-20a in two pancreatic carcinoma cell lines (BxPC-3 and Panc-1) and immortal human pancreatic duct epithelial cell line H6C7. Proliferation and invasion capacity were analyzed for the cells with lentivirus-mediated overexpression of microRNA-20a both in vitro and in vivo. In addition, the regulation of signal transducer and activator of transcription proteins 3 (Stat3) by microRNA-20a was determined to elucidate the underlying mechanisms. The pancreatic cancer cell lines (Panc-1 and BxPC-3) stably overexpressing microRNA-20a showed reduced proliferation and invasion capacity in vitro and in vivo, compared with parental cells or cells transfected with a control vector. Furthermore, we found that microRNA-20a negatively regulated Stat3 protein expression in a dose-dependent manner without changing the Stat3mRNA level and decreased the activity of a luciferase reporter construct containing the Stat3 3'-untranslated region. These results show that microRNA-20a regulates Stat3 at the post-transcriptional level, resulting in inhibition of cell proliferation and invasion of pancreatic carcinoma. It may open a new perspective for the development of effective gene therapy for pancreatic carcinoma.

引用

页码：1723 / 1734

页数：12

共 42 条

[1] Targeting signal-transducer-and-activator-of-transcription-3 for prevention and therapy of cancer - Modern target but ancient solution [J].

Aggarwal, Bharat B. ;

Sethi, Gautam ;

Ahn, Kwang Seok ;

Sandur, Santosh K. ;

Pandey, Manoj K. ;

Kunnumakkara, Ajaikumar B. ;

Sung, Bokyung ;

Ichikawa, Haruyo .

SIGNAL TRANSDUCTION PATHWAYS, PT B: STRESS SIGNALING AND TRANSCRIPTIONAL CONTROL, 2006, 1091 :151-169

[2] microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells [J].

Bandres, Eva ;

Bitarte, Nerea ;

Arias, Fernando ;

Agorreta, Jackeline ;

Fortes, Puri ;

Agirre, Xabi ;

Zarate, Ruth ;

Diaz-Gonzalez, Juan A. ;

Ramirez, Natalia ;

Sola, Jesus J. ;

Jimenez, Paula ;

Rodriguez, Javier ;

Garcia-Foncillas, Jesus .

CLINICAL CANCER RESEARCH, 2009, 15 (07) :2281-2290

[3] MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].

Bartel, David P. .

CELL, 2007, 131 (04) :11-29

[4] MicroRNA expression patterns to differentiate pancreatic adenocarcinoma from normal pancreas and chronic pancreatitis [J].

Bloomston, Mark ;

Frankel, Wendy L. ;

Petrocca, Fabio ;

Volinia, Stefano ;

Alder, Hansjuerg ;

Hagan, John P. ;

Liu, Chang-Gong ;

Bhatt, Darshna ;

Taccioli, Cristian ;

Croce, Carlo M. .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2007, 297 (17) :1901-1908

[5] STATs in oncogenesis [J].

Bowman, T ;

Garcia, R ;

Turkson, J ;

Jove, R .

ONCOGENE, 2000, 19 (21) :2474-2488

[6] Real-time quantification of microRNAs by stem-loop RT-PCR [J].

Chen, CF ;

Ridzon, DA ;

Broomer, AJ ;

Zhou, ZH ;

Lee, DH ;

Nguyen, JT ;

Barbisin, M ;

Xu, NL ;

Mahuvakar, VR ;

Andersen, MR ;

Lao, KQ ;

Livak, KJ ;

Guegler, KJ .

NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e179.1-e179.9

[7] Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines [J].

DeArmond, D ;

Brattain, MG ;

Jessup, JM ;

Kreisberg, J ;

Malik, S ;

Zhao, SJ ;

Freeman, JW .

ONCOGENE, 2003, 22 (49) :7781-7795

[8] Mapping lass of heterozygosity at chromosome 13q:: Loss at 13q12-q13 is associated with breast tumour progression and poor prognosis [J].

Eiriksdottir, G ;

Johannesdottir, G ;

Ingvarsson, S ;

Björnsdottir, IB ;

Jonasson, JG ;

Agnarsson, BA ;

Hallgrimsson, J ;

Gudmundsson, J ;

Egilsson, V ;

Sigurdsson, H ;

Barkardottir, RB .

EUROPEAN JOURNAL OF CANCER, 1998, 34 (13) :2076-2081

[9]

El-Rayes Basil F, 2003, Clin Adv Hematol Oncol, V1, P430

[10] miR-20a promotes proliferation and invasion by targeting APP in human ovarian cancer cells [J].

Fan, Xingxing ;

Liu, Yankun ;

Jiang, Jiechun ;

Ma, Zhuoya ;

Wu, Haidong ;

Liu, Tao ;

Liu, Min ;

Li, Xin ;

Tang, Hua .

ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2010, 42 (05) :318-324

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