Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2009 Aug;119(8):2119-23.
doi: 10.1172/JCI40107. Epub 2009 Jul 20.

MicroRNA reexpression as differentiation therapy in cancer

Prasun J Mishra  1 , Glenn Merlino
Affiliations
Comment

MicroRNA reexpression as differentiation therapy in cancer

Prasun J Mishra et al. J Clin Invest. 2009 Aug.

Abstract

Since their discovery in the early 2000s, microRNAs (miRNAs) and their penchant for RNA interference have taken the scientific community by storm, working their way into virtually every corner of biological inquiry. The very nature of their action, the ability to simultaneously extinguish the expression of a multitude of genes and negate their functions, immediately suggested therapeutic promise. In this issue of the JCI, a step toward the realization of this promise is described. Taulli et al. demonstrate that the miRNAs miR-1/miR-206, which are routinely lost in advanced, poorly differentiated rhabdomyosarcoma (RMS) but characteristically expressed in the mature skeletal muscle from which these tumors arise, restore the myogenic differentiation program and block the tumorigenic phenotype (see the related article beginning on page 2366). Their data support the notion that these small RNAs, effectively functioning as "micro-sheriffs" by restoring myogenic law and order, hold substantial clinical potential as differentiation therapy for RMS and perhaps other solid tumors. miRNA reexpression therapy constitutes a novel approach to handcuff oncogenes and arrest tumor development.

PubMed Disclaimer

Figures

Figure 1
Figure 1. A model describing miRNA reexpression as differentiation therapy in cancer.
Tissue-specific miRNAs play an important role in cell differentiation and are often deregulated in many human diseases, including cancer. Reexpressing such “micro-sheriff” miRNAs in a cell can deliver a dramatic impact, because miRNAs regulate a vast number of genes and pathways, including oncogenes and tumor suppressor genes. Tissue-specific tumor-suppressing miRNAs have the potential to promote the redifferentiation of tumor cells to their normal counterparts and solid malignancies to their original tissue types. The lung-specific miRNA pneumomiR-29, downregulated in non–small cell lung cancer (NSCLC), suppresses tumorigenicity by normalizing atypical patterns of methylation in non–small cell lung cancer cells (15). Taulli et al. now report in this issue of JCI that reexpression of myomiR-1/206 in RMS cells reduces oncogenic phenotypes and induces myogenic differentiation by downregulating cancer-associated genes and upregulating muscle-specific genes (12). Remarkably, introduction of striated muscle-specific myomiR-1 (downregulated in RMS) or brain-specific neuromiR-124 (downregulated in glioblastoma) into HeLa cells, a very well-characterized cervical carcinoma line, can shift the mRNA expression profile toward that of the tissue in which these miRNAs were originally enriched (3); this finding suggests that particularly powerful tissue-specific miRNAs may actually be able to drive virtually any cancer cell (shown here as a “generic tumor cell”) toward a specific differentiated state. Arrows on the right indicate the status of tissue-specific miRNA expression and the corresponding expression patterns of oncogenic genes and differentiation genes, which are opposing.
See this image and copyright information in PMC

Comment on

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. He L., Hannon G.J. MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 2004;5:522–531. doi: 10.1038/nrg1379. - DOI - PubMed
    1. Mishra P.J., Bertino J.R. MicroRNA polymorphisms: the future of pharmacogenomics, molecular epidemiology and individualized medicine. Pharmacogenomics. 2009;10:399–416. doi: 10.2217/14622416.10.3.399. - DOI - PMC - PubMed
    1. Lim L.P., et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005;433:769–773. doi: 10.1038/nature03315. - DOI - PubMed
    1. Chuang J.C., Jones P.A. Epigenetics and microRNAs. Pediatr. Res. 2007;61:24R–29R. doi: 10.1203/pdr.0b013e3180457684. - DOI - PubMed
    1. Calin G.A., Croce C.M. MicroRNA signatures in human cancers. Nat. Rev. Cancer. 2006;6:857–866. doi: 10.1038/nrc1997. - DOI - PubMed