The miRNA network: micro-regulator of cell signaling in cancer

Abstract

The dysregulation of cell signaling plays a pivotal role in tumorigenesis and progression. miRNAs have been linked to almost all known aspects of physiological and pathological processes. It is well known that the miRNA network is linked at several and unexpected levels with cancer-related signaling pathways. Our understanding of the roles and regulation of the miRNA network has been extended to include classical cell signaling, termed miRNA network complements cell signaling in cancer. As a transcription factor, tumor suppressor p53 plays a central role in tumor prevention. Recent studies have demonstrated that miRNAs may regulate the expression of the p53 pathway or be regulated by the p53 pathway. These findings added a new and challenging layer of complexity to the p53 pathway and prompted us to contemplate the use of the compensatory mechanisms in therapeutics against cancer. In this review, we have therefore summarized the p53 tumor suppressive pathway as a typical paradigm to elucidate the advances of the compensatory mechanisms. We then go on to critically discuss how the compensatory mechanisms can be used to enable better cancer diagnosis and prognosis and to serve as potential therapeutic targets.

Keywords::

• cell signaling
• gene regulation
• miRNAs
• p53 pathway
• prognosis
• tumorigenesis

Acknowledgements

The authors are grateful to the entire tumor group of Han’s Laboratory for help and support.

Financial & competing interests disclosure

The research related to this work in the authors’ laboratory was supported by the grants from the National Natural Science Foundation of China (No. 81101486, 81272867, 31270820 and 81230061) and is partially supported by National Basic Science and Development Programme of China (2010CB912802 and 2012CB518103). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

No writing assistance was utilized in the production of this manuscript.

Key issues

• miRNA network as a micro-regulator of classical cell signaling to regulate tumor formation and development. miRNAs can act as the effectors, catalysts and hindrances of the p53 pathway.

• The miRNA network crosstalks with cell signaling at multiple levels.

• The miRNA network adds another layer of complexity to cell signaling.

• miRNA is a prospective marker and target for cell signaling intervention therapy.