Downregulation of Pim-2 induces cell cycle arrest in the G 0 /G 1 phase via the p53-non-dependent p21 signaling pathway.

Pim-2 is a serine/threonine protein kinase that is highly expressed in various types of cancer, with essential roles in the regulation of signal transduction cascades, which promote cell survival and proliferation. The present study demonstrated that Pim-2 was expressed in cells lines derived from hematopoietic tumors and lung cancer. In vitro , downregulation of Pim-2 by short interfering RNA inhibited proliferation and delayed G0 /G1 cell cycle progression in K562 leukemia, RPMI-8226 multiple myeloma, and H1299 and A549 non-small cell lung carcinoma cell lines. Furthermore, downregulation of Pim-2 resulted in upregulation of cyclin-dependent kinase (CDK) inhibitor p21, irrespective of the p53 status. In addition, the present study revealed that CDK2 and phosphorylated retinoblastoma (pRb) were significantly downregulated. This finding suggested that inhibition of CDK2 and pRb expression via upregulated p21 was involved in the downregulation of Pim-2-induced G0 /G1 cell cycle arrest in lung cancer and hematopoietic malignancy cells. These results suggested that Pim-2 may serve a role in hematopoietic tumors, lung cancer proliferation and cell cycle progression by regulating the p21 signaling pathway. Downregulation of Pim-2 decreased cancer cell proliferation. Therefore, Pim-2 may be a potential therapy target in clinical cancer therapy.