Opposite Expression of HNRNPA2B1 in Cancer and Senescent Cells and Its Regulatory Role in Senescence of Cancer Cells / 中国生物化学与分子生物学报

ABSTRACT

Splicing factor Heterogeneous Nuclear Ribonucleoprotein A2/B1 (HNRNPA2B1 ) is associated with mouse lifespan and human longevity.It also plays a causal role in cancer development.However, whether it participates in cellular senescence, a biological process that contributes to individual aging and inhibits cancer, remains unknown.Here, we report that HNRNPA2B1 showed significantly increased expression in various cancer types while consistently decreased expression in multiple cellular senescence models.Knocking down HNRNPA2B1 in cancer cells leads to a series of senescence- associated phenotvpes.In line with its function as a splicing factor, HNRNPA2B1 downregulation causes alternative splicing changes in over one thousand genes, including those known to have a causal role in senescence.Our results also suggests that the E2F transcription factor 1 (E2F1 ) could regulate the expression of HNRNPA2BI, and E2F1-HNRNPA2B1 may be a new regulatory axis functioning in both cancer and cellular senescence, which might also have potential medical implications for cancer therapies.