miRNA in Cancer Pathway

Overview of miRNA in Cancer Pathway

MicroRNAs (miRNAs) are small non-coding RNAs with a length of 20–22 nucleotides that are involved in every biological pathway in multicellular organisms, including mammals . MiRNAs act as feedback mechanisms in normal physiological conditions, regulating critical biological processes such as cell proliferation, differentiation, and apoptosis . Deregulation of a single or small subset of miRNAs has been shown to have a profound effect on the expression pattern of several hundred messenger RNAs , accelerating cell transformation . The disease-associated miRNAs in humans, namely miR15 and miR16 at 13q14, were initially identified in chronic lymphocytic leukemia . Subsequently, it was discovered that patients with diffuse large B-cell lymphoma had elevated levels of tumor-associated miRNAs in their serum .

Numerous reports indicate that more than half of miRNA genes are located in regions of the genome associated with cancer or in fragile sites. Microarray data from a diverse range of cancer tissues/cells have demonstrated that aberrant miRNA expression is the norm rather than the exception. MiRNAs have been implicated and shown to play a role in a variety of cancers, including breast, colon, gastric, lung, prostate, and thyroid . The peer-reviewed scientific literature on miRNAs is massive, as evidenced by 15,943 PubMed hits in March 2015, and their role in cancer is extremely diverse, both in terms of disease and experimental approaches used by investigators. While the vast majority of published research focuses on a single mRNA target, the majority of miRNAs exert their effects by targeting multiple mRNAs, some of which may be located in the same cellular pathway. Additionally, several studies demonstrated that there were redundant with distinct sequences capable of repressing the same target mRNA . MiRNA overexpression or ablation in mouse models has established causal links between miRNAs and cancer development.

Microarray analysis of oligonucleotide miRNA is the most frequently used high-throughput technique for determining the levels of expression of hundreds of miRNA in a variety of cancer-specific cell types . MiRNA profiling studies have revealed significantly different miRNA profiles in cancer cells when compared to normal cells in the same tissue. Additionally, hierarchical clustering analyses indicated that miRNA signature profiling enabled the identification of a specific origin for tumor tissue samples. Numerous genome-wide profiling studies have been conducted on a variety of cancer types, including breast, chronic lymphocytic leukemia, colon, lung, glioblastoma, and thyroid papillary carcinoma, among others . MiRNA analysis revealed significantly dysregulated miR-125b, miR-145, miR-21, and miR-155 in 76 breast cancer and 10 normal breast tissue samples: 15 of these analyses correctly predicted whether the sample was normal or tumor breast tissue .