RASAL2 regulates the cell cycle and cyclin D1 expression through PI3K/AKT signalling in prostate tumorigenesis

Prostate cancer (PCa) growth and progression are uniquely dependent on androgens, making the androgen receptor pathway a prime target for therapy; however, cancer progression to androgen independence leads to treatment failure and poor prognosis. In recent years, alternative therapeutic pathways for PCa have been extensively explored, such as the PTEN/PI3K/AKT pathway, cell cycle, and DNA repair. In the present study, we discovered that RASAL2, a RAS-GTPase-activating protein, acted as an oncogene to regulate cancer cell proliferation and the cell cycle and contributed to tumorigenesis via the PI3K/AKT/cyclin D1 pathway. First, RASAL2 expression was higher in PCa tumour and metastatic lymph node tissues than in matched adjacent nontumor tissues and was associated with higher PCa tumour stage, Gleason score and poorer prognosis. Mechanistically, we found that RASAL2 promoted tumour cell proliferation, the transition from G1 to S phase in vitro and tumour growth in vivo. Furthermore, we demonstrated that RASAL2 facilitated phosphorylation of AKT, which in turn increased the expression of cyclin D1 encoded by the CCND1 gene. In addition, there was a positive correlation between the expression of RASAL2 and cyclin D1 in subcutaneous xenografts and clinical specimens. Taken together, these findings indicate that RASAL2 plays an oncogenic role in prostate cancer and may promote PCa tumorigenesis through PI3K/AKT signalling and cyclin D1 expression.

Automated summary

Prostate cancer growth and progression are dependent on androgens, but treatment failure and poor prognosis occur when the cancer becomes androgen independent. In this study, RASAL2 was found to play an oncogenic role in prostate cancer by promoting tumor cell proliferation and growth through the PI3K/AKT/cyclin D1 pathway. RASAL2 expression was higher in cancer tissues and correlated with poorer prognosis. These findings suggest that RASAL2 may be a potential therapeutic target for prostate cancer.