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

Abstract

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.

Proline-rich Protein 11 Overexpression is Associated With a More Aggressive Phenotype and Poor Overall Survival in Ovarian Cancer Patients

“…Moreover, the staining intensity of the PRR11 protein gradually increased along with the progression of OC, from low expression in benign tumors to intensive positivity in tumor emboli, which indicates that PRR11 may be used as an OC tumor biomarker. Previous studies have shown that PRR11 immunostaining can be found mainly in the cytoplasm as well as in the plasma membrane of OC cells [16]. In several of our pathological images, PRR11 IHC analysis showed a strong staining on the cell membrane, as well as in the cytoplasm, which was relatively weak, probably due to marginal effects and differences between tissues.…”

“…In addition, numerous genes and pathways have been found to be responsive in ovarian carcinogenesis or can be regarded as clinical predictors for disease recurrence and patient survival [23,24]. Zhu et al, previously reported that PRR11 participated in the progression and metastasis of OC through the PI3K / AKT / β-catenin signaling pathway [16]. However, the molecular mechanisms underlying the poor OS rates observed in OC patients with high PRR11expression remain unclear.…”

“…Moreover, PRR11 has been regarded as a potential biomarker target for cancer treatment in the future, as it exerts a strong association with a poor prognosis in human cancers, such as breast cancer [13], gastric cancer [14], and cholangiocarcinoma [15]. Despite evidence showing that PRR11 participates in the development of OC [16], the precise value of PRR11 in mediating the aggressive phenotype and poor overall survival (OS) in OC is still unclear.…”

Hub Genes of Stroke Identified by Weighted Gene Co-expression Network Analysis

“…PRR11 consists of a binary nuclear localization signal, two proline enrichment regions and a zinc nger domain, which regulates gene transcription by binding to duplex DNA [36]. Previous studies report that PRR11 is implicated in tumor progression.However, the role and clinical application value of PRR11 in stroke is unknown [36,37]. Studies show that Notch signaling in cerebral ischemia plays a role in in ammation, oxidative stress, apoptosis, angiogenesis, synaptic plasticity and the function of blood-brain barrier [38][39][40].…”

Biological and anti‐vascular activity evaluation of ethoxy‐erianin phosphate as a vascular disrupting agent

“…A cell migration and infiltration assay were executed in a Transwell chamber with Matrigel (BD Biosciences, San Diego, CA). Then, a density of 5 × 10 4 HUVECs in medium without FBS was added to an upper chamber or an upper chamber precoated with 60 μL Matrigel (1:7 dilution) . The lower chamber was filled with 600 μL medium containing 15% FBS.…”