MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance

Taiki Moriyama, Kenoki Ouchida, Kazuhiro Mizumoto, Jun Yu, Norihiro Sato, Toshinaga Nabae, Shunichi Takahata, Hiroki Toma, Eishi Nagai, Masao Tanaka

Research output: Contribution to journalArticle

264 Citations (Scopus)

Abstract

Due to the poor prognosis of pancreatic cancer, novel diagnostic modalities for early diagnosis and new therapeutic strategy are urgently needed. Recently, microRNA-21 (miR-21) was reported to be strongly overexpressed in pancreatic cancer as well as in other solid cancers. We investigated the functional roles of miR-21, which have not been fully elucidated in pancreatic cancer. miR-21 expression was assessed in pancreatic cancer cell lines (14 cancer cell lines, primary cultures of normal pancreatic epithelial cells and fibroblasts, and a human normal pancreatic ductal epithelial cell line) and pancreatic tissue samples (25 cancer tissues and 25 normal tissues) by quantitative real-time reverse transcription-PCR amplification. Moreover, we investigated the proliferation, invasion, and chemoresistance of pancreatic cancer cells transfected with miR-21 precursor or inhibitor. miR-21 was markedly overexpressed in pancreatic cancer cells compared with nonmalignant cells, and miR-21 in cancer tissues was much higher than in nonmalignant tissues. The cancer cells transfected with the miR-21 precursor showed significantly increased proliferation, Matrigel invasion, and chemoresistance for gemcitabine compared with the control cells. In contrast, inhibition of miR-21 decreased proliferation, Matrigel invasion, and chemoresistance for gemcitabine. Moreover, miR-21 positively correlated with the mRNA expression of invasion-related genes, matrix metalloproteinase-2 and -9, and vascular endothelial growth factor. These data suggest that miR-21 expression is increased in pancreatic cancer cells and that miR-21 contributes to the cell proliferation, invasion, and chemoresistance of pancreatic cancer.

Original languageEnglish
Pages (from-to)1067-1074
Number of pages8
JournalMolecular Cancer Therapeutics
Volume8
Issue number5
DOIs
Publication statusPublished - May 1 2009

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MicroRNAs
Pancreatic Neoplasms
gemcitabine
Neoplasms
Cell Line
Epithelial Cells
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Vascular Endothelial Growth Factor A
Reverse Transcription
Early Diagnosis
Fibroblasts
Cell Proliferation
Polymerase Chain Reaction
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. / Moriyama, Taiki; Ouchida, Kenoki; Mizumoto, Kazuhiro; Yu, Jun; Sato, Norihiro; Nabae, Toshinaga; Takahata, Shunichi; Toma, Hiroki; Nagai, Eishi; Tanaka, Masao.

In: Molecular Cancer Therapeutics, Vol. 8, No. 5, 01.05.2009, p. 1067-1074.

Research output: Contribution to journalArticle

Moriyama, Taiki ; Ouchida, Kenoki ; Mizumoto, Kazuhiro ; Yu, Jun ; Sato, Norihiro ; Nabae, Toshinaga ; Takahata, Shunichi ; Toma, Hiroki ; Nagai, Eishi ; Tanaka, Masao. / MicroRNA-21 modulates biological functions of pancreatic cancer cells including their proliferation, invasion, and chemoresistance. In: Molecular Cancer Therapeutics. 2009 ; Vol. 8, No. 5. pp. 1067-1074.
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