Pseudogene PLGLA exerts anti-tumor effects on hepatocellular carcinoma through modulating miR-324-3p/GLYATL1 axis

Background: Pseudogenes are dysfunctional copies of protein-coding genes that showed critical regulatory roles during carcinogenesis. Plasminogen like A (PLGLA) is a transcribed unprocessed pseudogene and biasedly expressed in liver. But its function has not been studied in hepatocellular carcinoma (HCC). Aims: We aimed to explore the role of PLGLA in HCC. Methods: The expression of PLGLA and its association with pathological features in HCC patients was analyzed using The Cancer Genome Atlas (TCGA) datasets. Quantitative reverse transcription PCR (qRTPCR) was used to validate PLGLA level in HCC tissue samples and cell lines. Gain-of-function experiments in vitro and in vivo were employed to assess the impact of PLGLA on HCC cell proliferation, migration and invasion. Luciferase reporter assay and RNA pull-down assay were conducted to confirm the interaction among PLGLA, miR-324-3p and GLYATL1. Results: PLGLA expression was significantly downregulated in HCC tissues and cell lines. Furthermore, low PLGLA expression was positively associated with tumor progression and poor prognosis. PLGLA restoration markedly suppressed cell proliferation, migration and invasion. Mechanistically, PLGLA could competitively bind to miR-324-3p and acted as a competitive endogenous RNA (ceRNA) to enhance GLYATL1 expression. Conclusions: Our results established a novel tumor suppressive role of PLGLA in HCC pathogenesis and highlighted its potential as a therapeutic target for HCC treatment. (C) 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.