SYNCRIP Modulates the Epithelial-Mesenchymal Transition in Hepatocytes and HCC Cells

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) control gene expression by acting at multiple levels and are often deregulated in epithelial tumors; however, their roles in the fine regulation of cellular reprogramming, specifically in epithelial–mesenchymal transition (EMT), remain largely unknown. Here, we focused on the hnRNP-Q (also known as SYNCRIP), showing by molecular analysis that in hepatocytes it acts as a “mesenchymal” gene, being induced by TGFβ and modulating the EMT. SYNCRIP silencing limits the induction of the mesenchymal program and maintains the epithelial phenotype. Notably, in HCC invasive cells, SYNCRIP knockdown induces a mesenchymal–epithelial transition (MET), negatively regulating their mesenchymal phenotype and significantly impairing their migratory capacity. In exploring possible molecular mechanisms underlying these observations, we identified a set of miRNAs (i.e., miR-181-a1-3p, miR-181-b1-3p, miR-122-5p, miR-200a-5p, and miR-let7g-5p), previously shown to exert pro- or anti-EMT activities, significantly impacted by SYNCRIP interference during EMT/MET dynamics and gathered insights, suggesting the possible involvement of this RNA binding protein in their transcriptional regulation.

Construction and validation of a prognostic marker and risk model for HCC ultrasound therapy combined with WGCNA identification

“…Synaptic binding protein-binding cytoplasmic RNA interaction protein (SYNCRIP) is an RNA-binding protein that is involved in regulating biological processes such as translation regulation, mRNA stabilization, pri-miRNAs processing, variable splicing, and miRNAs compartmentalization ( Mourelatos et al, 2001 ; Weidensdorfer et al, 2009 ; Geuens et al, 2016 ; Chen et al, 2020 ). Studies have shown that SYNCRIP expression can indicate a poor prognosis of HCC ( Uhlen et al, 2017 ), and SYNCRIP can stimulate the progression of HCC by controlling the epithelial-mesenchymal transition of HCC ( Riccioni et al, 2022 ). β-1,4-galactosyltransferase III (B4GALT3) belongs to the B4GALT family, and B4GALTs are capable of transferring galactose moieties from uridine diphosphate to oligosaccharides at the N-terminal end of acetylamino-glucose, which in turn forms acetylamino-lactose ( Guo et al, 2001 ).…”

Tumor-Promoting Actions of HNRNP A1 in HCC Are Associated with Cell Cycle, Mitochondrial Dynamics, and Necroptosis

“…However, the mechanism of HNRNP A1 in HCC has not been fully elucidated. Researchers detected that the upregulation of HNRNP A1 can promote HCC metastasis through facilitating the EMT and invasion/migration of HCC cells, and the loss of HNRNP A1 leads to reduced levels of EMT markers [ 28 , 29 , 30 , 31 ]. In our research, HNRNP A1 played a critical role in the proliferation, invasion, and migration of HCC cell lines, where HNRNP A1 was highly expressed.…”

Epithelial–Mesenchymal Transition (EMT) 2021

“…Riccioni and colleagues [ 11 ] show the role of hnRNP-Q (also known as SYNCRIP) as a positive modulator of EMT in hepatocytes, demonstrating that silencing of SYNCRIP induces MET, leading to inhibition of migration capacity of hepatocarcinoma cells. At the molecular level, they identify a panel of miRNAs, including miR-181-a1-3p, miR-181-b1-3p, miR-122-5p, miR-200a-5p, and miR-let7g-5p, which are regulated by SYNCRIP during EMT/MET dynamics.…”