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Small Molecule Targeting of a MicroRNA Associated with Hepatocellular Carcinoma.

Abstract：

:Development of precision therapeutics is of immense interest, particularly as applied to the treatment of cancer. By analyzing the preferred cellular RNA targets of small molecules, we discovered that 5"-azido neomycin B binds the Drosha processing site in the microRNA (miR)-525 precursor. MiR-525 confers invasive properties to hepatocellular carcinoma (HCC) cells. Although HCC is one of the most common cancers, treatment options are limited, making the disease often fatal. Herein, we find that addition of 5"-azido neomycin B and its FDA-approved precursor, neomycin B, to an HCC cell line selectively inhibits production of the mature miRNA, boosts a downstream protein, and inhibits invasion. Interestingly, neomycin B is a second-line agent for hepatic encephalopathy (HE) and bacterial infections due to cirrhosis. Our results provocatively suggest that neomycin B, or second-generation derivatives, may be dual functioning molecules to treat both HE and HCC. Collectively, these studies show that rational design approaches can be tailored to disease-associated RNAs to afford potential lead therapeutics.

journal_name

ACS Chem Biol

journal_title

ACS chemical biology

authors

Childs-Disney JL,Disney MD

doi

10.1021/acschembio.5b00615

subject

Has Abstract

pub_date

2016-02-19 00:00:00

pages

375-80

issue

2

eissn

1554-8929

issn

1554-8937

journal_volume

11

pub_type

杂志文章

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