The Genome Stability-Related lncRNA ZFPM2-AS1 Promotes Tumor Progression via miR-3065-5p/XRCC4 in Hepatocellular Carcinoma

Abstract

Abstract Long noncoding RNAs (lncRNAs) have a certain link to genomic stability (GS). However, the regulatory relationship of lncRNAs and GS has not been thoroughly investigated in hepatocellular carcinoma (HCC). We retrieved the TCGA samples that had somatic mutations and lncRNA expression data. The RNA levels were determined by quantitative polymerase chain reaction (qPCR) and protein levels were detected by Western blotting (WB). Cell counting kit 8 (CCK8) and colony formation assays were used to assess cell viability. Cell apoptosis and cell cycle progression were measured by flow cytometry. GS was detected by alkaline comet and chromosomal aberration assays. The xenograft model and lung metastasis model were used to assess the role of ZFPM2-AS1 in tumor growth in vivo. The molecular mechanism underlying the biological functions of ZFPM2-AS1 was investigated through bioinformatic prediction, RNA pull down and luciferase reporter assays. We identified 85 genomic instability-related lncRNAs and developed a prognostic model. The prognostic model showed good predictive power (area under the curve [AUC] = 0.797). ZFPM2-AS1 was significantly highly expressed in tumor tissues (P < 0.001), and it promoted DNA damage repair (P = 0.004) and tumor progression in vitro and in vivo. Luciferase reporter assays demonstrated that miR-3065-5p could bind directly with ZFPM2-AS1 and X-ray repair cross complementing 4 (XRCC4). ZFPM2-AS1 upregulated XRCC4 expression by acting as a sponge (P < 0.001). We developed and validated a prognostic model for HCC and experimentally investigated one lncRNA of its components. ZFPM2-AS1 in the model regulates XRCC4 by sponging miR-3065-5p to promote GS and HCC progression.