MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer

S. Hasegawa, H. Eguchi, H. Nagano, M. Konno, Y. Tomimaru, H. Wada, N. Hama, K. Kawamoto, S. Kobayashi, N. Nishida, J. Koseki, T. Nishimura, N. Gotoh, S. Ohno, N. Yabuta, H. Nojima, M. Mori, Y. Doki, H. Ishii

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

Background: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance.

Methods: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining.

Results: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients.

Conclusions: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.

Original languageEnglish
Pages (from-to)1572-1580
Number of pages9
JournalBritish journal of cancer
Volume111
Issue number8
DOIs
Publication statusPublished - Oct 14 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer'. Together they form a unique fingerprint.

  • Cite this

    Hasegawa, S., Eguchi, H., Nagano, H., Konno, M., Tomimaru, Y., Wada, H., Hama, N., Kawamoto, K., Kobayashi, S., Nishida, N., Koseki, J., Nishimura, T., Gotoh, N., Ohno, S., Yabuta, N., Nojima, H., Mori, M., Doki, Y., & Ishii, H. (2014). MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. British journal of cancer, 111(8), 1572-1580. https://doi.org/10.1038/bjc.2014.454