Opposite expression of HNRNPA2B1 in cancer and senescent cells and its regulatory roles in senescence of cancer cells

Splicing factor 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 led to a series of senescence-associated phenotypes. In line with its function as a splicing factor, HNRNPA2B1 downregulation caused alternative splicing changes in over one thousand genes, including those known to have a causal role in senescence. Our results also indicated that the transcription factor E2F1 could regulate the expression of HNRNPA2B1, 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.