Abstract
BackgroundThe 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.MethodsFirst 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.ResultsmiRNA-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).ConclusionsmiRNA-29c shows anti-tumorigenesis activity, and preoperative circulating miRNA-29c levels can be used to predict postoperative early relapse of CRC.
Highlights
The high incidence and mortality of colorectal cancer (CRC) pose a significant public health problem worldwide [1]
CRC early relapse was defined as local recurrence or distant metastasis that occurs within 1 year after radical resection [5,20,21] and the patients that relapsed after the first year and did not relapse during the time of the study were classified into the non-early relapsed group
Relapse was significantly associated with tumor type and perineural invasion (P,0.05, Table 2), but age, sex, tumor size, UICC stage of patients or histology distributions were not significantly different between early and non-early relapsed patients (P.0.05, Table 2)
Summary
The high incidence and mortality of colorectal cancer (CRC) pose a significant public health problem worldwide [1]. The time from the initial treatment to the development of recurrence has been reported to be strongly related to survival, in patients within one year of their surgical resection [5]. MiRNAs have been suggested to play roles in the development of cancers, including carcinogenesis, progression, and recurrence [7,8,9,10]. 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. We further investigated the functions and serum level of miRNA-29c in relation to early recurrence of CRC
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