Inhibition of MicroRNA Maturation Blocks Tumor Suppression

Two RNA-binding proteins, LIN28 and LIN28B, have been shown to promote cancer development by inhibiting the maturation of the let-7 family of tumor-suppressing microRNAs (miRNAs).

Investigators from Children's Hospital Boston (MA, USA) evaluated the activity of the genes for LIN28 and LIN28B in human primary tumors and human cancer cell lines. They reported in the May 31, 2009, online edition of the journal Nature Genetics that the two genes were overexpressed in these cells resulting in repression of the let-7 miRNA family.

Blockage of the tumor-suppressing activity of the let-7 miRNAs resulted in cells becoming more immature and stem-like qualities that made the cells more likely to become cancerous. This finding confirmed the results of previous studies that had shown that LIN28, which is abundant in embryonic stem cells and prevents them from differentiating into specific cell types, and the closely related LIN28B were involved in some 15% of human cancers.

"Linking this protein to advanced cancer is a very exciting new result,” said senior author Dr. George Daley, director of stem cell transplantation at Children's Hospital Boston. "It gives us a new target to attack, especially in the most resistant and hard-to-treat cases. LIN28 is a fascinating protein that acts both in stem cells and cancers, and is teaching us that cancer is often a disease of stem cells.”

The investigators are now looking for chemotherapeutic agents that would inhibit the activities of LIN28 and LIN28B.

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