Abstract
Lung cancer is the most frequent cause of cancer‑associated mortality worldwide. Upregulation of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) has been reported in non‑small cell lung cancer (NSCLC) cells, but its contribution to NSCLC remains poorly understood. hnRNPA2/B1 is involved in carcinogenesis by interacting with a number of proteins; however, little is known about its interaction with p53. The results of the present study revealed that hnRNPA2/B1 expression levels were upregulated in NSCLC cells under tumorsphere culture conditions and cisplatin treatment compared with those in cells under the adherent condition and dimethyl sulfoxide treatment, respectively, suggesting that hnRNPA2/B1 expression is induced under stress conditions. hnRNPA2/B1 knockdown decreased the number and size of NSCLC cell colonies in a clonogenic survival assay and led to a decreased migratory potential of NSCLC cells, suggesting that hnRNPA2/B1 may promote the survival, proliferation and migration of NSCLC cells. hnRNPA2/B1 knockdown induced G0/G1phase arrest in NSCLC cells through cyclinE degradation and phosphorylation of cyclin‑dependent kinase2. In addition, hnRNPA2/B1 knockdown inhibited extracellular signal‑regulated kinase(ERK)1/2 phosphorylation, suggesting that hnRNPA2/B1 may promote the G1/Sphase transition in NSCLC cells through ERK signaling. hnRNPA2/B1 knockdown resulted in increased expression levels of p21 and p27 in NSCLC cells, as well as p53 induction and phosphorylation. Additionally, hnRNPA2/B1 knockdown inhibited human double minute2 protein (HDM2) stability and phosphorylation, whereas overexpression of hnRNPA2 induced the opposite effects. These results suggested that hnRNPA2/B1 may promote the survival, proliferation and migration of NSCLC cells through preventing the activation of p53, which is induced by ERK‑mediated HDM2 activation. The results of the present study also indicated that the components of the hnRNPA2/B1/ERK/p53/HDM2 signaling pathway may be novel potential molecular targets for the treatment of patients with NSCLC.
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