MicroRNA-21 in Colorectal Cancer: “Just Another Brick in the Wall”?

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MicroRNAs (miRNAs)—small, noncoding RNA strands consisting of 18 to 25 base pairs—have been investigated extensively during the last decade. Initially seen as superfluous material, it has become clear that they play a critical role in translational and posttranscriptional regulation of protein processing. In cancer cells those processes are altered and cancer cells therefore display an irregular miRNA configuration. Many solid tumors have specific patterns of miRNA expression levels, which are used in several commercially available, and, in some cases, Food and Drug Administration approved, diagnostic tests. It is possible to determine tumor origin and, in part, the histologic subtype of solid tumors by its miRNA signature. Evaluating miRNA in tissue and body fluids is therefore an emerging field of biomarker development. MicroRNA 21 (miR-21) is found to be upregulated in a wide range of solid tumors including lung, breast, gastric, colon, and glioblastoma (1), and therefore as a single marker is not specific for colon cancer. Its reported RNA targets include transforming growth factor ß (TGF-ß), phosphatase and tensin homolog (PTEN), programmed cell death protein 4 (PDCD4), protein sprouty 1 (Spry-1), phosphatase of regenerating liver 3 (PRL-3), and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Therefore, miR-21 may be involved in the modulation of critical steps in carcinogenesis such as proliferation, apoptosis, and migration (2). It has further been shown that colon cancer cell lines with higher expression levels of miR-21 have an enhanced ability of motility and invasion (3). Slaby and others demonstrated that tissue miR-21 expression is rising with higher Union for International Cancer Control stage (4,5) and therefore represents a marker for clinicopathologic features of the disease. First data have been published to state a role of miR-21 in chemoresistance to gemcitabine in cholangiocellular cancer cell lines (6) and 5-fluorouracil in colon cancer cells (7). Higher miR-21 tissue levels could further be linked to a decreased pathologic tumor response in patients treated with FOLFOX in a neoadjuvant setting for locally advanced colorectal cancer (CRC) (8). Owing to its capability to be secreted by cancer cells, miR-21 has been the first miRNA to be detected in the plasma in patients with diffuse large B-cell lymphoma in 2008 (9). These specifics taken together, miR-21 represents an almost ideal candidate for a diagnostic tool in the diagnosis and treatment monitoring of CRC.