Clinical correlations of miR-21 expression in colorectal cancer patients and effects of its inhibition on DLD1 colon cancer cells

Int J Colorectal Dis. 2012 Nov;27(11):1401-8. doi: 10.1007/s00384-012-1461-3. Epub 2012 Apr 3.

Abstract

Purpose: MicroRNA-21 (miR-21) is one of the miRNAs that are frequently and highly overexpressed in tumor tissue of colorectal cancer (CRC) patients; however, only a little is known about its functional role in CRC.

Methods: We examined the expression level of miR-21 in 44 paired samples of tumoral and non-tumoral colon tissues diagnosed for CRC using TaqMan real-time PCR method. Furthermore, we used miR-21 inhibitor (anti-miR-21) to transient knockdown of miR-21 in DLD-1 colon cancer cells and examined the effects of miR-21 silencing on viability, apoptosis, chemosensitivity, cell cycle, and migration of DLD1 cells.

Results: The expression levels of miR-21 were significantly increased in CRC tumor tissue (P < 0.0001). Significant differences in miR-21 levels were observed also between CRC tissues of patients with CRC in different clinical stages: I vs. II (P = 0.033) and I vs. IV (P = 0.021). Kaplan-Meier analysis proved that the miR-21 expression levels are correlated to shorter overall survival of CRC patients (P = 0.0341). MiR-21 silencing in DLD1 cell line had no effect on the cell viability; however, when combined with chemotherapeutics (5-FU, L-OHP, and SN38), it contributed to the decrease of cell viability. Suppression of miR-21 decreased cell migration ability of DLD-1 cells by nearly 30 % (P = 0.016).

Conclusion: We have confirmed the overexpression of miR-21 in CRC samples and its correlation with advanced disease and shorter overall survival. These findings could be described in part by the fact that CRC cells with increased expression of miR-21 have higher migration ability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cell Cycle / drug effects
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged

Substances

  • Antineoplastic Agents
  • MIRN21 microRNA, human
  • MicroRNAs