LncRNA ZNF667-AS1: A Promising Therapeutic Target for Colorectal Cancer by Regulating PNRC2-Mediated Cell Proliferation, Invasion and Apoptosis.

Abstract

Background: Long non-coding RNA (lncRNA) zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) is closely related to the advancement of a variety of cancers, but its functional role in colorectal cancer remains unclear. This study was designed to explore the function and molecular mechanisms of lncRNA ZNF667-AS1 in colorectal cancer.

Methods: Reverse transcriptase real-time quantitative polymerase chain reaction (RT-qPCR) was used for the detection of ZNF667-AS1 and proline-rich nuclear receptor co-activator protein 2 (PNRC2) expression level. Cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU), and colony formation assays were conducted to assess cell proliferation; flow cytometry and transwell invasion assay were performed separately to measure cell apoptosis and invasion. RNA immunoprecipitation (RIP) assay was utilized to analyze the relationship between ZNF667-AS1 and PNRC2. Western blot was to test the PNRC2 protein expression. The in vivo role of ZNF667-AS1 in the advancement of colorectal cancer was evaluated by tumor xenograft assay.

Results: LncRNA ZNF667-AS1 and PNRC2 were both decreased in colorectal cancer tissue samples and cells (p < 0.05). ZNF667-AS1 overexpression remarkably restrained proliferation and invasion in HCT-116 and LOVO cells, but enhanced cell apoptosis (p < 0.0001). Moreover, ZNF667-AS1 directly targeted PNRC2, and positively regulated its expression. The influence of ZNF667-AS1 overexpression on invasion, apoptosis, and proliferation was suppressed by PNRC2 knockdown in HCT-116 and LOVO cells. Additionally, ZNF667-AS1 overexpression markedly inhibited tumor growth via upregulation of PNRC2 in mice in vivo (p < 0.05).

Conclusion: LncRNA ZNF667-AS1 expressed low in colorectal cancer. LncRNA ZNF667-AS1 repressed proliferation and invasion, and enhanced apoptosis of colorectal cancer cells by targeting PNRC2.