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Cancer: Decoding the noncoding

In a recent study, Lin Zhang and his colleagues identify an oncogenic long noncoding RNA (lncRNA), FAL1, that may contribute to the progression of a number of different cancers (Cancer Cell 26, 344–357, 2014).

The authors analyzed single nucleotide polymorphism arrays of 2,394 tumor specimens from 12 cancer types and, using the genomic locations of 13,780 lncRNAs, calculated the somatic copy number alteration frequency of each locus. lncRNAs were defined as oncogenic if they were found in at least 25% of specimens of any single tumor type, were located in a focal amplicon and could be detected in more than half of the 40 cell lines tested. Of the oncogenic lncRNAs identified, the group went on to verify that FAL1 contributed to clonogenicity and proliferation of cell lines derived from multiple tumor types.

Credit: Steve Gschmeissner / Science Source

In patient samples, FAL1 copy number gain was more frequent in epithelial tumors, compared to hematopoietic and neural tumors. Furthermore, in ovarian cancer samples, FAL1 RNA levels and genomic gain were associated with decreased survival. The authors found that FAL1 associates with BMI1, inhibiting the proteasomal degradation of the protein and leading to altered expression of MBI1 target genes, including CDKN1A (encoding the cyclin-dependent kinase inhibitor p21). Intraperitoneal FAL1 siRNA injection decreased tumor growth in the A2780 orthotopic ovarian cancer model, concomitant with an increase in p21.

This study suggests that targeting the lncRNA FAL1 may be beneficial in cancer treatment, particularly for ovarian tumors.

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Simpson, K. Cancer: Decoding the noncoding. Nat Med 20, 1105 (2014). https://doi.org/10.1038/nm.3725

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