Purpose: Long noncoding RNAs are differentially expressed in hepatocellular carcinoma (HCC) and have been validated as essential regulators in HCC. However, there is limited knowledge regarding the detailed roles and mechanisms of most lncRNAs in HCC cells. In this study, the expression profiles of PRR34 antisense RNA 1 (PRR34-AS1 ) in HCC tissues and cell lines were determined. In addition, the detailed roles and underlying mechanisms of PRR34-AS1 in HCC cells were comprehensively elucidated.
Methods: Reverse transcription-quantitative polymerase chain reaction (PCR) was performed to measure PRR34-AS1  expression in HCC cells. Cell proliferation, apoptosis, and migration and invasion were evaluated in vitro using the cell counting kit-8 (CCK-8) assay, flow cytometric analysis, and transwell cell migration and invasion assays, respectively. In vivo tumor growth was determined using tumor xenograft experiments. The potential miRNA targets of PRR34-AS1  were predicted via bioinformatic analysis and further confirmed using the luciferase reporter assay, RNA immunoprecipitation assay, and reverse transcription-quantitative PCR.
Results: PRR34-AS1  was highly expressed in HCC tissues and cell lines, and its interference suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis in vitro. In addition, loss of PRR34-AS1  decreased tumor growth in HCC cells in vivo. Mechanistically, PRR34-AS1 functions as a miR-498  sponge and subsequently increases forkhead box O3 (FOXO3 ) expression in HCC cells. Rescue experiments revealed that the suppressive effects triggered by PRR34-AS1  knockdown on the malignant characteristics of HCC cells could be abrogated by inhibiting miR-498  or restoring FOXO3  expression.
Conclusion: The depletion of PRR34-AS1  suppresses the oncogenicity of HCC cells by targeting the miR-498/FOXO3 axis. Therefore, the PRR34-AS1/miR-498/FOXO3 pathway may offer a basis for HCC treatment.
Keywords: PRR34 antisense RNA 1, forkhead box O3, ceRNA regulation model, polymerase chain reaction