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LINC02802 Acts as an Oncogene Role by Stabilizing IQGAP1 Protein Level in Hepatocellular Carcinoma
Vol 37, Issue 9, 2023
Abstract
Background: Copy number amplification of genomic Chromosome 1q21.1 has emerged as a robust predictor of overall survival in hepatocellular carcinoma (HCC) patients. However, the study of functional long non-coding RNA (lncRNA)s located in 1q21.1 remains unclear. Here, we reported that LINC02802 in Chr 1q21.1 loci exhibit oncogenic roles in HCC patients. Methods: We analyzed the copy-number gains or RNA expression levels of LINC02802 by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in HCC samples. Loss- or gain-of-function assays were carried out to determine the biological effects on cell growth and metastasis in vitro and in vivo. Furthermore, mass spectrometry analysis from biotinylated LINC02802 pulldown assays revealed that IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a prominent binding partner of LINC02802 in HCC cells. Results: The progression of HCC cells is robustly mitigated by LINC02802 knockdown and significantly aggravated by its overexpression. Mechanistically, we found that elevated RNA levels of LINC02802 have directly interacted with the polyproline protein-protein domain, the four IQ motifs domain, and the Ras GTPase-activating protein-related domain of IQGAP1. This interaction stabilizes IQGAP1 by disrupting its interactions with tripartite-motif-containing protein 56 (TRIM56). As a consequence, the ubiquitination-mediated degradation of IQGAP1 is inhibited. Conclusions: LINC02802, an oncogene, has significant potential as a prognostic biomarker, and targeting LINC02802 could provide a promising therapeutic strategy for HCC patients.
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Copyright (c) 2023 Wen Zhang, Jiejing Yu, Jiao Wang, Yaming Xu, Shibo Zhang, Jiawen Jiang, Yuang Chen, Xuyu Zhao, Hui Dong, Li Yang, Robert Chunhua Zhao, Wei Dong, Zhe Li
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Medical Genetics, University of Torino Medical School, Italy

Department of Biomedical, Surgical and Dental Sciences, University of Milan, Italy