Abstract
This study determined the expression of microRNA-133a (MiR-133a) in colorectal cancer (CRC) and adjacent normal mucosa samples and evaluated its clinicopathological role in CRC. The expression of miR-133a in 125 pairs of tissue samples was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and correlated with patient's clinicopathological data by statistical analysis. Endogenous expression levels of several potential target genes were determined by qRT-PCR and correlated using Pearson's method. MiR-133a was downregulated in 83.2% of tumors compared to normal mucosal tissue. Higher miR-133a expression in tumor tissues was associated with development of distant metastasis, advanced Dukes and TNM staging, and poor survival. The unfavorable prognosis of higher miR-133a expression was accompanied by dysregulation of potential miR-133a target genes, LIM and SH3 domain protein 1 (LASP1), Caveolin-1 (CAV1), and Fascin-1 (FSCN1). LASP1 was found to possess a negative correlation (γ = −0.23), whereas CAV1 exhibited a significant positive correlation (γ = 0.27), and a stronger correlation was found in patients who developed distant metastases (γ = 0.42). In addition, a negative correlation of FSCN1 was only found in nonmetastatic patients. In conclusion, miR-133a was downregulated in CRC tissues, but its higher expression correlated with adverse clinical characteristics and poor prognosis.
Highlights
Alone, colorectal cancer (CRC) is responsible for 600,000 mortalities annually and approximately 1.2 million new cases are reported each year [1]
Among the 125 samples, 104 (83.2%) cancers displayed low miR-133a expression; of the other 21 tumors, 4 (3.2%) tumors displayed upregulated miR-133a expression and 17 (13.6%) tumors displayed no change in expression compared to adjacent nontumor mucosa, suggesting that miR-133a repression was frequently observed in CRC patients
In patients who did not develop metastases, there was a significant negative correlation between FSCN1 and miR-133a expression (Figure 2(f), γ = −0.33, P = 0.037), but no significant association was observed in patients with metastatic disease. These results indicated the complex mechanism of target genes regulated by miR-133a, in which the miR-133a regulatory effect was opposite to that reported in other studies (CAV1), or even within CRC of different metastatic potential (CAV1 and FSCN1)
Summary
Colorectal cancer (CRC) is responsible for 600,000 mortalities annually and approximately 1.2 million new cases are reported each year [1]. This makes CRC the 3rd most common cancer worldwide and the 2nd leading cause of cancer-related deaths in Europe and USA [2]. In approximately 20% of cases, there is a strong genetic component involved as first-degree relatives are diagnosed with the same cancer or they have an underlying genetic predisposition (e.g., diabetes mellitus, obesity, gender, and inflammatory bowel disease) that increases the risk of CRC. Diet with high intake of alcohol, red-meat and fat, and insufficient fiber uptake increases the risk for CRC [4]
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