Paraoxonase‐2 shRNA‐mediated gene silencing suppresses proliferation and migration, while promotes chemosensitivity in clear cell renal cell carcinoma cell lines

Abstract Clear cell renal cell carcinoma (ccRCC) represents the most common subtype of renal tumor. Despite recent advances in identifying novel target molecules, the prognosis of patients with ccRCC continues to be poor, mainly due to the lack of sensitivity to chemo‐ and radiotherapy and because of one‐third of renal cell carcinoma patients displays metastatic disease at diagnosis. Thus, identifying new molecules for early detection and for developing effective targeted therapies is mandatory. In this work, we focused on paraoxonase‐2 (PON2), an intracellular membrane‐bound enzyme ubiquitously expressed in human tissues, whose upregulation has been reported in a variety of malignancies, thus suggesting its possible role in cancer cell survival and proliferation. To investigate PON2 involvement in tumor cell metabolism, human ccRCC cell lines were transfected with plasmid vectors coding short harpin RNAs targeting PON2 transcript and the impact of PON2 silencing on cell viability, migration, and response to chemotherapeutic treatment was then explored. Our results showed that PON2 downregulation was able to trigger a decrease in proliferation and migration of ccRCC cells, as well as an enhancement of cell sensitivity to chemotherapy. Thus, taken together, data reported in this study suggest that the enzyme may represent an interesting therapeutic target for ccRCC.