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MicroRNAs (miRNAs) are small (21-23 nucleotides in length) single stranded RNA molecules which are not translated into proteins but whose main function is to regulate gene expression. Almost all types of tumour have abnormal – usually reduced – miRNA expression, and scientists at Johns Hopkins Medical School, Nationwide Children’s Hospital, and Ohio State University have now shown that replacing missing miRNAs in mice with liver cancer can rapidly kill the tumour cells whilst leaving healthy cells untouched. The team found that hepatocellular carcinoma (HCC) cells had reduced levels of miR-26a, a miRNA that is normally expressed at high levels in a variety of tissues. In vitro, expression of miR-26a in liver cancer cells was shown to cause cell-cycle arrest associated with direct targeting of cyclins D2 and E2. Systemic administration of miR-26a to mice with HCC using an adeno-associated virus vector inhibited the proliferation of the cancer cells and protected the animals from disease progression. Normal liver cells were unaffected by the treatment. After three weeks, 8 out of 10 mice treated with the miRNA showed only small tumours or a complete absence of tumours, whereas 6 out of 8 sham-treated mice experienced aggressive disease progression.

The study shows that liver cancer can be successfully treated in an animal model of disease by replacing ‘missing’ miRNA using a delivery vector that is suitable for use in the clinic. Although more work is needed before the technique could be used in patients, it could provide an effective and safe treatment for human HCCs, which account for 80 – 90% of all liver cancers and generally have a poor prognosis. If suitable delivery systems can be developed, the technique could also be used to treat other diseases caused by ‘missing’ miRNA.

The study is published in the June 12^th edition of Cell.

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