The role of lncRNA LINP1 in the DNA-repair pathway

Researchers from the University of Pennsylvania recently reported the discovery of a long noncoding RNA (lncRNA) termed lncRNA in non-homologous end joining (NHEJ) pathway 1 (LINP1), that serves as an RNA scaffold interacting with Ku70–Ku80 and DNA-PKcs, promoting NHEJ repair. LINP1 was identified as overexpressed in triple-negative breast cancers (TNBCs) when compared with other breast cancer subtypes using RNA-seq data from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia (CCLE). LINP1 knockdown enhanced apoptosis in TNBC cell lines following doxorubicin treatment, a chemotherapy drug for TNBC, while overexpression of LINP1 in an estrogen-receptor positive breast cancer (ER+ BC) cell line with undetectable LINP1 protected these cells from doxorubicin-induced apoptosis. These findings have profound implications for our general understanding of the mechanism of DNA DSB repair by NHEJ.

LINP1 regulation and role in the NHEJ DNA-repair pathway


LINP1 expression levels are positively and negatively regulated by the EGF and p53 signaling pathways, respectively. On recognition of DNA DSBs by the Ku70–Ku80 complex, LINP1 and DNA-PKcs are recruited to form a synaptic complex joining the broken DNA ends and initiating DNA repair. NHEJ inhibitors currently evaluated in anti-cancer clinical trials in combination with radiotherapy are indicated, with miR-29 mimetics potentially offering a novel therapeutic avenue.

Sakthianandeswaren A, Liu S, Sieber OM. (2016) Long noncoding RNA LINP1: scaffolding non-homologous end joining. Cell Death Discov 2:16059. [article]

Leave a Reply

Your email address will not be published. Required fields are marked *