The tumor-suppressive and potential therapeutic functions of miR-34a in epithelial carcinomas

ABSTRACT

Introduction: Many RNA species have been identified as important players in the development of chronic diseases including cancer. Certain classes of regulatory RNAs such as microRNAs (miRNAs) have been investigated in such detail that bona fide tumor suppressive and oncogenic miRNAs have been identified. Because of this, there has been a major effort to therapeutically target these small RNAs. One in particular, a liposomal formulation of miR-34a (MRX34), has entered Phase I trials.

Areas covered: This review aims to summarize miRNA biology, its regulation within normal versus disease states and how it can be targeted therapeutically, with a particular emphasis on miR-34a. Understanding the complexity of a single miRNA will aid in the development of future RNA-based therapeutics for a broader range of chronic diseases.

Expert opinion: The potential of miRNAs to be developed into anti-cancer therapeutics has become an increasingly important area of research. miR-34a is a tumor suppressive miRNA across many tumor types through its ability to inhibit cellular proliferation, invasion and tumor sphere formation. miR-34a also shows promise within certain in vivo solid tumor models. Finally, as miR-34a moves into clinical trials it will be important to determine if it can further sensitize tumors to certain chemotherapeutic agents.

KEYWORDS:

• Biomarker
• breast cancer
• cancer
• lung
• microRNA
• miR-34
• therapy
• treatment resistance
• tumor suppressor
• cancer

Article highlights

• MicroRNAs, in particular miR-34a, are key players in both the regulation of normal biological processes and in the development of cancer.

• miR-34a is involved in the differentiation of megakaryocytes and granulocytes, providing a crucial check on uncontrolled proliferation.

• miR-34a is downregulated in a wide range of human cancers, and both in vitro and in vivo studies indicate that miR-34a functions as a tumor suppressor.

• miR-34a can function effectively in combination with traditional chemotherapeutics.

• The broad tumor suppressive nature of miR-34a indicates that it holds great potential as a therapeutic agent.

This box summarizes key points contained in the article.

Acknowledgments

We thank Eleni Anastasiadou and Catherine O Adams for the critical reading of this manuscript.

Declaration of interest

FJ Slack is supported by the National Institutes of Health through the award [numbers R01 CA157749 and R01 CA131301]. FJ Slack is also an advisor to and shareholder in Mirna Therapeutics, Inc. 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.