The functional significance of microRNA-29c in patients with colorectal cancer: a potential circulating biomarker for predicting early relapse

PLoS One. 2013 Jun 28;8(6):e66842. doi: 10.1371/journal.pone.0066842. Print 2013.

Abstract

Background: The recurrence of colorectal cancer (CRC) is frequent within the first year of curative resection surgery and may be unavoidable. microRNAs have been suggested to play roles in carcinogenesis and cancer recurrence. We recently identified microRNA-29c (miRNA-29c) as a predictor of early recurrence in CRC. In the present study, we further investigated the functions and serum level of miRNA-29c in relation to early recurrence of CRC.

Methods: First we further confirmed overexpression of miRNA-29c in non-early relapse subjects. Gain-of-function in vitro studies were used to evaluate the effect of miRNA-29c on cell proliferation, migration, invasion, and cell cycle progression. The colon cancer cell line Caco2 and a stable clone overexpressing miRNA-29c were xenografted to evaluate the in vivo effect of miRNA-29c in null mice. Finally, circulating miRNA-29c was investigated as a potential biomarker for identifying early relapse.

Results: miRNA-29c expression significantly decreased during early relapse compared to non-early relapse in UICC stage II and III CRC patients (P = 0.021). In vitro studies showed that overexpression of miRNA-29c inhibited cell proliferation and migration. The cell cycle studies also revealed that miRNA-29c caused an accumulation of the G1 and G2 population. In vivo, miRNA-29c suppressed tumor growth in null mice. The serum miRNA-29c increased significantly in early relapsed patients compared to non-early elapsed patients (P = 0.012).

Conclusions: miRNA-29c shows anti-tumorigenesis activity, and preoperative circulating miRNA-29c levels can be used to predict postoperative early relapse of CRC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / blood*
  • Caco-2 Cells
  • Case-Control Studies
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood*
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasm Transplantation
  • Treatment Failure
  • Tumor Burden
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN29a microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by grants from the National Science Council of the Republic of China (NSC 99-2320 B-037-014-MY3); Kaohsiung Medical University Hospital (KMUH98-8I04, KMUH100-OR16); Biosignature in Colorectal Cancers, Academia Sinica, Taiwan; and an Excellence for Cancer Research Center Grant funded by the Department of Health, Executive Yuan, Taiwan, Republic of China (DOH102 TD-C-111-002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.