Oncogenic KRAS regulates miR-200c and miR-221/222 in a 3D-specific manner in colorectal cancer cells

Toshiyuki Tsunoda, Yasuo Takashima, Yasuhiro Yoshida, Keiko Doi, Yoko Tanaka, Takahiro Fujimoto, Takashi Machida, Takeharu Ota, Midori Koyanagi, Masahide Kuroki, Takehiko Sasazuki, Senji Shirasawa

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Background: Oncogenic KRAS plays several key roles in a three-dimensional (3D) colonic-crypt model. However, miRNA expression regulated by oncogenic KRAS in this model is still elusive. Materials and Methods: The differential expression of 105 cancer-related microRNAs was examined and compared in HCT116 cells and HKe3 cells (HCT116 cells in which mutated KRAS allele was deleted) in 3D culture. HKe3 cells stably overexpressing oncogenic KRAS and the public datasets for microRNA expression analysis of colorectal cancer were further examined. Results: The increased expression of miR-200c, miR-221 and miR-222 were observed exclusively in 3D culture, but not in the two-dimensional culture. These microRNAs were regulated by oncogenic KRAS and were significantly overexpressed in human colorectal tumor specimens. Of note, the protein expression level of Phosphatase and tensin homolog (PTEN), a putative target of miR-221/222 cluster, was reduced under the control of oncogenic KRAS in a 3D-specific manner. Conclusion: Oncogenic KRAS regulates 3D-specific molecules, possibly being associated with colorectal tumor development in vivo.

Original languageEnglish
Pages (from-to)2453-2459
Number of pages7
JournalAnticancer research
Volume31
Issue number7
Publication statusPublished - Jul 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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