MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9

Shin Hamada, Kennichi Satoh, Wataru Fujibuchi, Morihisa Hirota, Atsushi Kanno, Jun Unno, Atsushi Masamune, Kazuhiro Kikuta, Kiyoshi Kume, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

125 Citations (Scopus)

Abstract

The epithelial-mesenchymal transition (EMT) is a critical step for pancreatic cancer cells as an entry of metastatic disease. Wide variety of cytokines and signaling pathways are involved in this complex process while the entire picture is still cryptic. Recently, miRNA was found to regulate cellular function including EMT by targeting multiple mRNAs. We conducted comprehensive analysis of miRNA expression profiles in invasive ductal adenocarcinoma (IDA), intraductal papillary mucinous adenoma, intraductal papillary mucinous carcinoma, and human pancreatic cancer cell line to elucidate essential miRNAs which regulate invasive growth of pancreatic cancer cells. Along with higher expression of miR-21 which has been shown to be highly expressed in IDA, reduced expression of miR-126 in IDA and pancreatic cancer cell line was detected. The miR-126 was found to target ADAM9 (disintegrin and metalloproteinase domain-containing protein 9) which is highly expressed in pancreatic cancer. The direct interaction between miR-126 and ADAM9 mRNA was confirmed by 3′ untranslated region assay. Reexpression of miR-126 and siRNA-based knockdown of ADAM9 in pancreatic cancer cells resulted in reduced cellular migration, invasion, and induction of epithelial marker E-cadherin. We showed for the first time that the miR-126/ADAM9 axis plays essential role in the inhibition of invasive growth of pancreatic cancer cells.

Original languageEnglish
Pages (from-to)3-10
Number of pages8
JournalMolecular Cancer Research
Volume10
Issue number1
DOIs
Publication statusPublished - 2012 Jan

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'MiR-126 acts as a tumor suppressor in pancreatic cancer cells via the regulation of ADAM9'. Together they form a unique fingerprint.

Cite this