PRR11 Overexpression Facilitates Ovarian Carcinoma Cell Proliferation, Migration, and Invasion Through Activation of the PI3K/AKT/β-Catenin Pathway.

BACKGROUND/AIMS: Ovarian cancer (OC) is the most lethal gynecologic malignancy, mainly due to the advanced stage at diagnosis in most patients and high rate of relapse. Thus, it is still essential to elucidate the underlying mechanisms and explore the diagnostic and therapeutic targets of OC. Recent studies have revealed that proline-rich protein 11 (PRR11) is dysregulated in different cancers, participating in their initiation and progression; however, it remains unclear whether PRR11 is involved in OC.

METHODS

Immunohistochemical staining, quantitative reverse transcription PCR, and western blotting were performed to evaluate PRR11 expression in OC tissues and cells. The relationship between PRR11 expression and the clinicopathologic data of patients were analyzed. We upregulated and downregulated PRR11 expression using a PRR11 overexpression vector and PRR11-specifc small interfering RNA, respectively, to further clarify its role in the malignant biological behavior of OC in vitro.

RESULTS

Overexpression of PRR11 in OC tissues and cells significantly correlated with advanced FIGO stage, lymph node metastasis, and large tumor size. Downregulation of PRR11 inhibited cell proliferation and prevented the invasion and migration of HO-8910 OC cells, whereas opposite results were observed in Caov3 cells upon PRR11 upregulation. Further analyses showed that PRR11 positively regulated cell proliferation-related proteins, including c-myc and cyclin D1, and increased and decreased the expression of matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2, respectively. Additionally, our preliminary results demonstrated that PRR11 expression was mediated by the phosphoinositide 3-kinase/AKT/β-catenin signaling pathway.

CONCLUSION

The results of this study provide evidence that PRR11 plays a critical role in the progression and metastasis of OC, and as such, may serve as a potential prognostic and therapeutic target in OC.