Decreased Expression of Retinoblastoma Protein-Interacting Zinc-Finger Gene 1 Is Correlated with Poor Survival and Aggressiveness of Cervical Cancer Patients

Abstract

Background: Retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) is a tumor suppressor deregulated in several human cancers. We aimed to explore RIZ1 expression status in FIGO stages I–II cervical cancer tissues, the association of RIZ1 expression with the clinical outcome of cervical cancer patients, and the role of RIZ1 in the proliferation, apoptosis, migration, and invasion of cervical cancer cells. Methods: The expression of RIZ1 in 268 cervical cancer tissues was assessed by immunohistochemistry, real-time PCR, and immunoblotting. RIZ1 was ectopically overexpressed in HeLa and SiHa cells. MTT assay, Annexin V staining, flow cytometry, wound healing assay, and Transwell assay were used to assess cell proliferation, apoptosis, migration, and invasion. Results: RIZ1 expression generally decreased in cervical cancer tissues. Decreased RIZ1 expression was significantly correlated with advanced FIGO stage (P=0.005), deep stromal invasion (P=0.001), lymphovascular space involvement (P=0.041), pelvic lymph node metastasis (P=0.005), and postoperative recurrence (P=0.002). Kaplan–Meier analysis demonstrated that patients with low RIZ1 expression had shorter overall survival and disease-free survival (DFS) than those with high RIZ1 expression. Multivariate analysis showed that RIZ1 was an independent prognostic factor for DFS (HR=2.184 (95%CI,1.365-3.496), p=0.001) and OS (HR=1.899 (95%CI,1.112-3.241), p=0.019) of cervical cancer patients. Ectopic overexpression of RIZ1 inhibited the proliferation, migration, and invasion, but promoted the apoptosis of HeLa and SiHa cells in vitro. Conclusion: Downregulation of RIZ1 expression may contribute to the tumor progression and poor survival of cervical cancer patients. RIZ1 may be a prognostic biomarker for cervical cancer patients. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81672584, 81602664, 81872460, 81372786), Natural Science Foundation of Heilongjiang Province (ZD2016016), Research project grant of Harbin Medical University Cancer Hospital (JY2016-05). Declaration of Interest: All the authors declare that there are no conflicts of interest. Ethical Approval: This study complied with the Helsinki Declaration and was approved by the Ethics Committee of Harbin Medical University (Harbin, China). Informed consents were obtained from all patients or their family members.