MicroRNA-29b is a Novel Prognostic Marker in Colorectal Cancer

Akira Inoue, Hirofumi Yamamoto, Mamoru Uemura, Junichi Nishimura, Taishi Hata, Ichiro Takemasa, Masakazu Ikenaga, Masataka Ikeda, Kohei Murata, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori

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Abstract

Purpose: Recent studies have suggested that microRNA-29 (miR-29) family members may play important roles in human cancer by regulating cell proliferation, differentiation, apoptosis, migration, and invasion. The present study aimed to investigate the clinical significance and biological function of miR-29b in colorectal cancer (CRC). Methods: Real-time polymerase chain reaction was used to quantify miR-29b expression. The association between miR-29b and survival was evaluated in 245 patients with CRC. We transfected an miR-29b mimetic into CRC cells to explore the functional role of miR-29b in vitro, based on a proliferation assay, flow cytometry, and Western blotting. Results: In clinical samples of CRC, miR-29b expression was significantly reduced in tumor tissues compared with normal mucosa (p < 0.012). Multivariate survival analyses indicated that miR-29b expression was an independent prognostic factor for disease-free survival (p = 0.026), lymph node metastasis (p = 0.004), and pathological T classification (p = 0.002). In a multivariate analysis of 5-year overall survival, we found a similar association between lymph node metastasis, pathological T classification, venous invasion, and miR-29b expression (p = 0.013). In vitro, low Ki-67-positive staining showed that administration of the mimic-miR-29b reduced proliferation of CRC cells. An Annexin V apoptosis assay and flow cytometric analysis revealed that miR-29b induced apoptosis and arrested the cell cycle at the G1/S transition. Moreover, miR-29b inhibited the expression of MCL1 and CDK6. Conclusions: Our findings indicated that miR-29b may be a useful, novel, prognostic marker and may play important roles in regulating apoptosis and cell cycle in CRC

Original languageEnglish
Pages (from-to)1410-1418
Number of pages9
JournalAnnals of Surgical Oncology
Volume22
DOIs
Publication statusPublished - Dec 1 2015
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Inoue, A., Yamamoto, H., Uemura, M., Nishimura, J., Hata, T., Takemasa, I., ... Mori, M. (2015). MicroRNA-29b is a Novel Prognostic Marker in Colorectal Cancer. Annals of Surgical Oncology, 22, 1410-1418. https://doi.org/10.1245/s10434-014-4255-8