MicroRNAs: Predictors and modifiers of chemo- and radiotherapy in different tumour types

Abstract 

MicroRNAs (miRNAs) represent a class of naturally occurring small non-coding RNA molecules. They regulate gene expression at the post-transcriptional level and control thereby cellular mechanisms including developmental transitions, organ morphology, apoptosis and cell proliferation. As might be expected from molecules with these roles, miRNAs are involved in cancer development, and deregulation of several miRNAs has been found in various cancer types. Some miRNAs modulate expression of known oncogenes or tumour suppressor genes whereas others function as so called onco-miRs or tumour-suppressor-miRs. Recently, miRNAs have been studied as potential diagnostic or therapeutic targets in cancer treatment. There is increasing interest in an association between miRNA expression in tumours and chemo- and radiosensitivity, both with regards to predicting or modulating sensitivity. And indeed, different miRNAs have been found to predict sensitivity to anticancer treatment: miR-30c, miR-130a and miR-335 are downregulated in various chemoresistant cell lines, hsa-Let-7g and hsa-miR-181b are strongly associated with response to 5-fluorouracil-based antimetabolite S-1. In addition, several miRNAs were shown to influence sensitivity to chemo- or radiotherapy: miRNAs of the Let-7 family induced radiosensitivity in vitro/in vivo, inhibition of miR-21 and miR-200b increased sensitivity to gemcitabine in cholangiocarcinoma cell lines, and restoration of miR-34 in p53-deficient human gastric cancer cells induced chemosensitisation. This article summarises the current literature describing the impact of miRNAs on prediction and modification of anticancer treatment including the possible intracellular pathways involved in these processes.

Keywords: Chemoresistance, Chemosensitivity, Radioresistance, Radiosensitivity, Chemotherapy, Radiotherapy, miRNA, MicroRNA