Versatile applications of microRNA in anti-cancer drug discovery: from therapeutics to biomarkers.
Over the past several years, microRNAs (miRNAs) have been identified as a fine-tuner in a wide array of biological processes, including development, cell growth and metabolism. Recent studies have shown that many kinds of miRNAs act as oncomirs or tumor suppressors in tumors where the miRNA genes are up- or down- regulated, respectively. These dysregulations occur through a variety of mechanisms, such as genetic alterations, epigenetic repression or altered expression of transcription factors which target miRNAs. The aberrant expressions of miRNAs are observed not only in tumor lesions but also in plasma and serum of cancer patients. These characteristics of miRNAs have created extensive interest in tapping into them for diagnosis and prognosis as well as drug discovery in cancer therapy. In this literature, the significance of miRNAs in tumor initiation and development is first reviewed. Second topic is extracellular miRNAs as biomarkers for cancer classification and prediction. Further, we focus on secretory machinery of miRNAs and share new evidence suggesting that extracellular miRNAs can play biological roles beyond mere biomarkers. Extending this concept, our hypothetical model that extracellular miRNAs may function as a signaling molecule in a crosstalk between cancer cells and their surrounding cells is presented. Finally, we discuss the potential of miRNAs for therapeutic applications in clinical oncology.
Iguchi
Haruhisa
H
Section for Studies on Metastasis, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Kosaka
Nobuyoshi
N
Ochiya
Takahiro
T
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000008:administration & dosage / Q000378:metabolism*; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D011379:Prognosis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D035683:MicroRNAs