Knockdown of microRNA-21 Inhibits Proliferation and Increases Cell Death by Targeting Programmed Cell Death 4 (PDCD4) in Pancreatic Ductal Adenocarcinoma

被引:84
作者
Bhatti, Imran [1 ]
Lee, Andrew [1 ]
James, Victoria [2 ]
Hall, Richard I. [1 ]
Lund, Jonathan N. [1 ]
Tufarelli, Cristina [1 ]
Lobo, Dileep N. [3 ]
Larvin, Michael [1 ]
机构
[1] Univ Nottingham, Med Sch Derby, Royal Derby Hosp, Div Surg,Sch Grad Entry Med & Hlth, Derby DE22 3DT, England
[2] Univ Nottingham, Sch Med, Queens Med Ctr, Sch Biomed Sci, Nottingham NG7 2UH, England
[3] Univ Nottingham Hosp, Queens Med Ctr, Div Gastrointestinal Surg, Nottingham Digest Dis Ctr NIHR Biomed Res Unit, Nottingham NG7 2UH, England
关键词
Pancreatic cancer or neoplasm or tumour; microRNA; miR-21; PDCD4; Carcinogenesis; Diagnosis; Prognosis; Biomarker; Cell culture; TUMOR-SUPPRESSOR PDCD4; HUMAN CHOLANGIOCARCINOMA; GASTRIC CARCINOMAS; HUMAN CANCERS; EXPRESSION; GENE; INVASION; SURVIVAL; MIR-21; GROWTH;
D O I
10.1007/s11605-010-1381-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
This study aims to examine the expression of a panel of five microRNAs (miRNA) in pancreatic ductal adenocarcinoma (PDAC) and the functional effect of miR-21 inhibition in PDAC cell lines. miRNA are short, non-coding RNA molecules, which play important roles in several cellular processes by silencing expression of their target genes through translational repression or mRNA degradation. They are often aberrantly expressed in cancer, and this dysregulation can promote carcinogenesis by altering the expression of tumour suppressor or oncogenes. miRNA expression levels were measured in 24 PDAC tumour/matched adjacent normal tissue samples and three PDAC cell lines using reverse transcription polymerase chain reaction. Levels of cell proliferation and death and expression of programmed cell death 4 (PDCD4; tumour suppressor) were studied in PDAC cells (MIA-Pa-Ca-2) in the absence or presence of a miR-21 inhibitor. PDAC primary tissues and cell lines displayed a consistent upregulation of miR-21 (P < 0.0001) and downregulation of both miR-148a (P < 0.0001) and miR-375 (P < 0.0001) relative to adjacent normal tissue. Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P < 0.0001). Inhibition of miR-21 in MIA-Pa-Ca-2 PDAC cells led to reduced cell proliferation (P < 0.01) and increased cell death (P < 0.01), with simultaneous increase in levels of the tumour suppressor, PDCD4 (P < 0.01). miRNA expression profiles may be used as biomarkers for detecting pancreatic cancer. Moreover, miR-21 could be a predictor of disease progression and a possible therapeutic target in part by upregulating PDCD4 in pancreatic cancer.
引用
收藏
页码:199 / 208
页数:10
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