MicroRNA-21 promotes proliferation, migration, and invasion of colorectal cancer, and tumor growth associated with down-regulation of sec23a expression

BMC Cancer. 2016 Aug 5:16:605. doi: 10.1186/s12885-016-2628-z.

Abstract

Background: MicroRNA-21 (miR-21) is up-regulated in many cancers, including colorectal cancer (CRC). Nevertheless, the function of miR-21 in CRC and the mechanism underlying that function is still unclear.

Methods: After analyzing the expression of miR-21 and Sec23A in CRC cell lines, we transfected the highest miR-21 expressing cell line, SW-480, with a plasmid containing an miR-21 inhibitor and the lowest miR-21 expressing cell line, DLD-1, with a plasmid containing an miR-21 mimic and measured the effects on the expression of Sec23A and on cell proliferation, migration, and invasion. We also evaluated the effect of knocking down Sec23A on miR-21 expression and its effects on cell proliferation, migration, and invasion. Finally, we assessed the effect of miR-21 in a xenograft tumor model in mice. Tumor tissues from these mice were subjected to immunohistochemical staining to detect the expression of Sec23A.

Results: Genetic deletion of miR-21 suppressed the proliferation, migration, and invasion of SW-480 cells, while over-expression of miR-21 promoted proliferation, migration, and invasion of DLD-1 cells. Inhibition of miR-21 increased the expression of Sec23A protein in SW-480 cells while over-expression of miR-21 significantly suppressed the expression of Sec23A protein and Sec23A mRNA in DLD-1 cells. Knockdown of Sec23A increased the expression of miR-21 in SW480 and DLD-1 cells and their proliferation (DLD-1 only), migration, and invasion. Over-expression of miR-21 promoted tumor growth in BALB/c nude mice and suppressed tumor expression of Sec23A.

Conclusion: These findings provide novel insight into the molecular functions of miR-21 in CRC, which may serve as a potential interesting target.

Keywords: Colorectal cancer; Proliferation; Sec23A; Tumor growth; miR-21.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation* / genetics
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / pathology*
  • Disease Progression
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Heterografts
  • Humans
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Vesicular Transport Proteins / biosynthesis*
  • Vesicular Transport Proteins / genetics

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • SEC23A protein, human
  • Vesicular Transport Proteins