Enhanced wild-type p53 expression by small activating RNA dsP53-285 induces cell cycle arrest and apoptosis in pheochromocytoma cell line PC12.

Abstract

Malignant pheochromocytoma (PHEO) is diagnosed only when metastasis has occurred, making it less likely for patients to obtain the benefits of traditional chemotherapy. Anti-oncogene TP53 mutation has been detected in PHEO and is possibly related to disease progression. However, whether the upregulation of wild-type TP53 has antitumoral effects on PHEO remains completely unknown. In the present study, we used RNA activation (RNAa) technique to upregulate the expression of wild-type TP53 by transfecting synthetic dsP53‑285 into PHEO cell line PC12. We found that the upregulation of wild-type p53 blocked the transition of PC12 cells from the G0/G1 to the Sphase, with induction of apoptosis. Additionally, the above-mentioned findings were attested invivo. Most importantly, dsP53-285-induced antitumoral effects were reversible following co-transfection with siRNA that targeted p53mRNA. Collectively, our results revealed that the upregulation of p53 and possibly other anti-oncogenes may provide a potential effective therapeutic strategy for PHEO.