Abstract
BackgroundMicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. However, its diagnostic value and role in CRC have yet to be described. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion.MethodsMature miR-133b and CXCR4 expression levels were detected in 31 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 6 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). Luciferase reporter assays and Western blots were used to validate CXCR4 as a putative target gene of miR-133b. Regulation of CXCR4 expression by miR-133b was assessed using qRT-PCR and Western blot analysis, and the effects of exogenous miR-133b and CXCR4 on cell invasion and migration were evaluated in vitro using the SW-480 and SW-620 CRC cell lines.ResultsA significant downregulation of miR-133b was observed in 93.55% of CRC tissues, and the expression of miR-133b was much lower in metastatic tumors (stage C and D, stratified by the Modified Dukes Staging System) than in primary tumors (stage A and B). In contrast, CXCR4 protein expression significantly increased in 52.63% of CRC samples, and increased CXCR4 expression in CRC was associated with advanced tumor stage. CXCR4 was shown to be a direct target of miR-133b by luciferase reporter assays, and transfection of miR-133b mimics inhibited invasion and stimulated apoptosis of SW-480 and SW-620 CRC cells.ConclusionsOur study demonstrated that downregulated miR-133b contributed to increased cell invasion and migration in CRC by negatively regulating CXCR4. These findings may be significant for the development of therapy target for CRC.
Highlights
Colorectal cancer (CRC) is the third most common cancer in males and the second most common cancer in females worldwide and has high incidence and mortality rates [1]
Decreased expression of miR-133b in human CRC showed significant diagnostic potential To investigate whether the expression level of this musclespecific miRNA was associated with disease progression, we first conducted quantitative RT-PCR (qRT-PCR) analyses to detect miR-133b expression in 31 human CRC tissues and their 19 counterparts from non-neoplastic adjacent tissues
A receiver operating characteristic (ROC) curve analysis was performed using the relative expression of miR-133b, and the associated area under the curve (AUC) was used to confirm the diagnostic potency of the miRNA
Summary
Colorectal cancer (CRC) is the third most common cancer in males and the second most common cancer in females worldwide and has high incidence and mortality rates [1]. Reports have increasingly shown the potential of using miRNAs as novel diagnostic markers and therapeutic targets [4,7,8,9]. MicroRNA-133b (miR-133b), which is a muscle-specific microRNA, has been reported to be downregulated in human colorectal carcinoma (CRC) when compared to adjacent non-tumor tissue. CXC chemokine receptor-4 (CXCR4), which participates in multiple cell processes such as cell invasion-related signaling pathways, was predicted to be a potential target of miR-133b. The aim of this study was to investigate the associations and functions of miR-133b and CXCR4 in CRC initiation and invasion
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