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New link established between the biological clock and the genesis of clear cell kidney cancer

Chi Van Dang

An October study published in Cell Reports led by Ludwig Institute Scientific Director Chi Van Dang and former graduate student Rebekah Brooks uncovered a new link between the biological clock and cancer. Rebekah, Chi and colleagues found that ADIRF-AS1, a long noncoding RNA that oscillates every 24 hours, drives a type of kidney cancer by inhibiting a tumor suppressor named PBAF. The tumor suppressor is one of three multi-subunit components of a giant protein complex (named SWI/SNF) that modifies chromatin to regulate gene expression. The SWI/SNF complex is mutated in various ways in about 20% of all cancers. ADIRF-AS1, meanwhile, is known to interact with PBAF in a type of bone cancer cell and, as it happens, one of the components of PBAF is mutated in 40% of clear cell renal carcinomas. Rebekah, Chi and team therefore explored the effects of the ADIRF-AS1 interaction with PBAF in clear cell kidney cancer. They showed that CRISPR-mediated genome editing to delete ADIRF-AS1 caused dampening of many genes associated with the biological clock that oscillate daily and completely suppressed the growth of clear cell kidney cancer in mice. The studies also suggest that ADIRF-AS1 has a function independent of PBAF that involves the extracellular matrix, or the molecular stuffing that surrounds cells.

Circadian lncRNA ADIRF-AS1 binds PBAF and regulates renal clear cell tumorigenesis
Cell Reports, 2022 October 18

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