Dicer and miRNA in relation to clinicopathological variables in colorectal cancer patients

Division of Biomedicine, Systems Biology Research Centre, School of Life Sciences, Skövde University, SE-541 28, Skövde, Sweden.
BMC Cancer (Impact Factor: 3.36). 08/2011; 11(1):345. DOI: 10.1186/1471-2407-11-345
Source: PubMed


Dicer is aberrantly expressed in several types of cancers. Applying real-time PCR, we detected the expression of Dicer mRNA in normal mucosa (n = 162), primary colorectal cancer (CRC) (n = 162) and liver metastasis (n = 37), and analysed the relationship between Dicer expression and clinicopathological features. We also correlated the expression of Dicer mRNA to the miRNA expression of miR-141, miR-200a, miR-200b, mir-200c and miR-429 in liver metastases.
RT-PCR and qPCR were used to analyse the Dicer expression in normal mucosa, primary tumour and liver metastasis by using the High Capacity cDNA Reverse Transcription Kit and TaqMan™® Gene Expression assays for Dicer and GAPDH. RT-PCR and qPCR were used to detect miRNA expression in liver metastases by utilizing TaqMan® MicroRNA Reverse Transcription Kit and TaqMan® miRNA Assays. Statistical analyses were performed with STATISTICA.
Dicer expression in rectal cancer (3.146 ± 0.953) was higher than in colon cancer (2.703 ± 1.204, P = 0.018). Furthermore the Dicer expression was increased in primary tumours (3.146 ± 0.952) in comparison to that in normal mucosa from rectal cancer patients (2.816 ± 1.009, P = 0.034) but this is not evident in colon cancer patients. Dicer expression in liver metastases was decreased in comparison to that of either normal mucosa or primary tumour in both colon and rectal cancers (P < 0.05). Patients with a high Dicer expression in normal mucosa had a worse prognosis compared to those with a low Dicer expression, independently of gender, age, tumour site, stage and differentiation (P < 0.001, RR 3.682, 95% CI 1.749 - 7.750). In liver metastases, Dicer was positively related to miR-141 (R = 0.419, P = 0.015).
Dicer is up-regulated in the early development of rectal cancers. An increased expression of Dicer mRNA in normal mucosa from CRC patients is significantly related to poor survival independently of gender, age, tumour site, stage and differentiation.

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    • "We identified indels in the pre-miRNA sequences of several miRNAs that have been linked to cancers. For example, the precursor of miR-558, which has been previously linked with aggressive neuroblastoma [33], contained 5 indels, and an indel (rs34385807) is located the pre-miRNA sequence of miR-141, which is involved in cancer proliferation [34], [35], [36], [37] and has been shown to target the tumor suppressor PTEN [38]. Additional precursor sequences of miRNAs containing indels include miR-520h [39], [40], [41], miR-486 [42], miR-489 [43], miR-223 [44], miR-373 [45], miR-630 [46] and miR-1233 [17], which have been shown to be involved in cancer development, and miR-631, which is associated with risk of coronary artery disease [47]. "
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    • "Table 1 summarizes these alterations based on experimental data from patients. MiRNome signatures revealed that miRNA affected many tumor-suppressive and oncogenic pathways implicated in CRC pathobiology, including β-catenin/Wnt signaling (miR-135a, -135b, -139, -145) [38•, 39, 40], apoptosis (miR-34a, -133b, -195) [38•, 41], differentiation (miR-141, -200c) [42–44], p53 signaling (miR-34b/c) [45], proliferation (K-RAS signaling: let7 family, miR-18a, -143, -200c) [38•, 41, 46], cell cycle control (miR-34a, -192, -215, -675) [38•, 41, 47], and migration, invasion, and metastasis (miR-126, -143, -196a, -200a, -200b, -200c, -373, -520c) [38•, 41, 44]. MiRNA pathway may also modulate DNA methylation (miR-143, -342) [48, 49]. "
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