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Acta Biochimica et Biophysica Sinica Advance Access originally published online on March 31, 2009
Acta Biochimica et Biophysica Sinica 2009 41(5):407-413; doi:10.1093/abbs/gmp023
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Genetic variation of miRNA sequence in pancreatic cancer

Zheng Zhu1,{dagger}, Wentao Gao2,{dagger}, Zhuyin Qian2,* and Yi Miao2,*

1 Department of General Surgery, The First Clinic Medical College of Nanjing Medical University, Nanjing 210029, China
2 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China

* Correspondence address. Tel: +86-25-83718836; Fax: +86-25-83724440; E-mail: qianzhusilver{at}163.com (Z.Q.) & miaoyi{at}njmu.edu.cn (Y.M.)


  Abstract

MicroRNAs (miRNAs) are small non-coding RNAs of 20–22 nucleotides (nts) and constitute a novel class of gene regulators that negatively regulate gene expression at the post-transcriptional level. The expression of miRNA is deregulated in many types of cancers. Alterations in miRNA expression may be an important contributor to the development of pancreatic carcinoma. We hypothesized that genetic variations in miRNA genes were associated with pancreatic carcinoma and analyzed genomic sequences coding for the precursors of eight miRNA genes in both pancreatic carcinoma tissues and cancer cell lines. Four novel mutations in primary miRNA transcripts were identified. TaqMan miRNA assays showed that miR-21 was significantly overexpressed in 20 pancreatic carcinomas and 6 cancer cell lines compared with paired benign tissues and normal pancreas. Two mutations of miR-21 did not notably alter the activity of the promoter of the miRNA gene. Although most of these mutations seem to have no effect on miRNA processing, an A–G mutation at 29-nt downstream of pre-miR-21 led to a conformational change of the secondary structure close to the stem reaching into the pre-miR-21 and a relative reduction of the mature miR-21 expression in vivo. These results suggested that miRNA might play an important role in pancreatic tumorigenesis, but the molecular mechanism underlying the particular sequence variations in miRNA that can cause aberrant expression remains to be determined.

Keywords    microRNAs; pancreatic cancer; promoter; secondary structure

Received: November 23, 2008; Accepted: March 10, 2009

{dagger}These authors contributed equally to this work.


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