MiR-622 inhibited colorectal cancer occurrence and metastasis by suppressing K-Ras

Mol Carcinog. 2016 Sep;55(9):1369-77. doi: 10.1002/mc.22380. Epub 2015 Aug 31.

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with many oncogenes and anti-oncogenes involved. MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that can adjust downstream targets. Accumulating evidence has revealed that microRNAs govern the occurrence and development of cancer. Here, we studied the role of miR-622 in CRC and clarified the underlying mechanism. We detected that miR-622 was down-regulated in colorectal tumor tissues and cell lines and that miR-622 was lower in metastatic CRC tissues compared with that in non-metastatic specimens. Furthermore, we confirmed that miR-622 inhibited tumor proliferation and migration in vitro. Through dual-luciferase reporter assay, we found kirsten rat sarcoma (K-Ras) gene was the direct target of miR-622. More importantly, K-Ras overexpression can rescue the inhibitory effect of miR-622 on CRC development. All these data were validated in colon xenograft tumor model. MiR-622-K-Ras signal pathway was a potentially new direction in the development of screening target and therapeutic treatments for CRC. © 2015 Wiley Periodicals, Inc.

Keywords: K-Ras; colorectal cancer; metastasis; miR-622.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colon / metabolism
  • Colon / pathology*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / pathology
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Rectum / metabolism
  • Rectum / pathology*

Substances

  • KRAS protein, human
  • MIRN622 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins p21(ras)