Demystification of CLSPN multiple potentialities in hepatocellular carcinoma: insight into individualized diagnosis and precision therapeutics

CLSPN, an essential molecule of the S-phase checkpoint in DNA replication stress, have not been elucidated in hepatocellular carcinoma (HCC). In this study, we firstly discovered and systematically verified CLSPN expression using RT-qPCR and western blotting assay, and its high expression was an independent prognostic factor in HCC. Patients with CLSPN low-expression had higher infiltration levels of T cell CD4 + memory resting, monocyte, mast cell activated, dryness index and lower immune response in HCC. Then, CLSPN silencing inhibited the proliferation, migration, invasion and cell cycle progression of HCC cells proved by CCK-8, transwell and cell cycle assay. We established a key lncRNA PSMA3-AS1/hsa-miR-101-3p/CLSPN regulator axis in HCC. Furthermore, CLSPN-mediated ubiquitination or deubiquitination may regulate post-transcriptional modifications in HCC. The emerging CLSPN potentialities might be mediated by the β-catenin-mediated Wnt signaling pathway. In addition, we detected CLSPN interaction protein profile, which further confirmed CLSPN involved in posttranscriptional modification, protein turnover, and biogenesis locating in cytoplasm, secreted, and mitochondrion. Therefore, it was the first time to discover and verify expression, prognosis, immunotherapy, RNAs regulator, posttranscriptional modification, and molecular mechanisms of CLSPN in HCC. These novel insights might accelerate the process of individualized diagnosis and precision therapeutics for patients with HCC.