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

• Published in: PloS one Vol. 8; no. 6; p. e66842
• Main Authors: Yang, I-Ping, Tsai, Hsiang-Lin, Huang, Ching-Wen, Huang, Ming-Yii, Hou, Ming-Feng, Juo, Suh-Hang Hank, Wang, Jaw-Yuan
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.06.2013; Public Library of Science (PLoS)
• Subjects: Adult; Aged; Aged, 80 and over; Animals; Apoptosis; Biology; Biomarkers; Biomarkers, Tumor - blood; Caco-2 Cells; Cancer; Cancer therapies; Carcinogenesis; Carcinogens; Case-Control Studies; Cell Cycle; Cell migration; Cell Movement; Cell Proliferation; Clinical medicine; Colon; Colon cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - blood; Colorectal Neoplasms - pathology; Colorectal Neoplasms - surgery; Community colleges; Disease-Free Survival; Female; Gene expression; Humans; In vivo methods and tests; Lung cancer; Male; Medical prognosis; Medicine; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; MicroRNAs - blood; Middle Aged; miRNA; Neoplasm Recurrence, Local - blood; Neoplasm Recurrence, Local - prevention & control; Neoplasm Transplantation; Patients; Prostate cancer; Ribonucleic acid; RNA; Studies; Surgery; Treatment Failure; Tumor Burden; Tumorigenesis; Xenografts; Young Adult; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0066842

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