Emerging role for R-loop formation in hepatocellular carcinoma

The pathophysiological characteristics of hepatocellular carcinoma (HCC) is closely associated with genomic instability. Genomic instability has long been considered to be a hallmark of both human genetic disease and cancers. It is now well accepted that regulating R-loop formation to minimized levels is one of critical modulation to maintain genome integrity, and that improper regulation of R-loop metabolism causes genomic instability via DNA breakage, ultimately resulting in replicative senescence and even tumorigenesis. Given that R-loop is natural by-product formed during normal transcription condition, and that several types of cancer have defense mechanism against the genomic instability resulted from R-loop formation, modulating functional implication of proteins involved in the intrinsic and specific mechanisms of abnormal R-loop formation in cancers therefore could play an important part in appropriated therapeutic strategies for HCC cohorts. In this review, we highlight the latest understanding on how R-loops promote genomic instability and address how alterations in these pathways link to human HCC.