MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma

TLDR: expression patterns of microRNAs are systematically altered in colon adenocarcinomas and high miR-21 expression is associated with poor survival and poor therapeutic outcome.

Abstract: COLON ADENOCARCINOMA IS A major cause of cancer mortality worldwide1 Colorectal cancer is the third most common and second leading cause of cancer death in the United States2 Even though 5-year mortality rates have modestly declined over the last 3 decades,3 there is still a need to identify new prognostic biomarkers and therapeutic targets for this disease Currently, chemotherapy has significant therapeutic value, but surgery is the only curative form of treatment4 Ideal therapeutic targets should be causally associated with disease and amenable to designing therapeutic interventions, whereas ideal biomarkers should be easy to measure and have strong associations with clinical outcomes MicroRNAs could match both criteria5-8 MicroRNAs are 18- to 25-nucleotide, noncoding RNA molecules that regulate the translation of many genes9 Since their discovery,10,11 microRNAs have been found to regulate a variety of cellular processes including apoptosis,12-14 differentiation,10,11,15 and cell proliferation16 MicroRNAs may also have a causal role in carcinogenesis5,17,18 MicroRNA expression levels are altered in most tumor types,19,20 including colon tumors20-23 Experimental manipulation of specific microRNAs modulates tumor development in mouse-model systems16,24-26 The prognostic potential of microRNAs has also been demonstrated for chronic lymphocytic leukemia,6 lung cancer,7 pancreatic cancer,27 and neuroblastomas28 If aberrant microRNA expression is causal to carcinogenesis, inhibiting specific microRNAs may have therapeutic implications Modified antisense oligonucleotides can easily be designed to specifically inhibit microRNA function29 Antagomirs are one type of antisense oligonucleotide that has proven effective at inhibiting microRNA function in vivo in mice30 The ease of designing specific inhibitors of microRNA function makes them candidates for therapeutic targets Given the therapeutic and prognostic potential for microRNAs in cancer, we evaluated microRNA profiles of colon tumors and paired nontumorous tissue to study their potential role in tumor formation, diagnosis, and response to chemotherapy in colon carcinoma