Posttranscriptional Inhibition of Protein Tyrosine Phosphatase Nonreceptor Type 23 by Staphylococcal Nuclease and Tudor Domain Containing 1: Implications for Hepatocellular Carcinoma.

Oncoprotein staphylococcal nuclease and tudor domain containing 1 (SND1) regulates gene expression at a posttranscriptional level in multiple cancers, including hepatocellular carcinoma (HCC). Staphylococcal nuclease (SN) domains of SND1 function as a ribonuclease (RNase), and the tudor domain facilitates protein-oligonucleotide interaction. In the present study, we aimed to identify RNA interactome of SND1 to obtain enhanced insights into gene regulation by SND1. RNA interactome was identified by immunoprecipitation (IP) of RNA using anti-SND1 antibody from human HCC cells followed by RNA immunoprecipitation sequencing (RIP-Seq). Among RNA species that showed more than 10-fold enrichment over the control, we focused on the tumor suppressor protein tyrosine phosphatase nonreceptor type 23 (PTPN23) because its regulation by SND1 and its role in HCC are not known. PTPN23 levels were down-regulated in human HCC cells versus normal hepatocytes and in human HCC tissues versus normal adjacent liver, as revealed by immunohistochemistry. In human HCC cells, knocking down SND1 increased and overexpression of SND1 decreased PTPN23 protein. RNA binding and degradation assays revealed that SND1 binds to and degrades the 3'-untranslated region (UTR) of PTPN23 messenger RNA (mRNA). Tetracycline-inducible PTPN23 overexpression in human HCC cells resulted in significant inhibition in proliferation, migration, and invasion and