miR-876 Inhibits EMT and Liver Fibrosis via POSTN to Suppress Metastasis in Hepatocellular Carcinoma

Abstract

Background. The asymptomatic onset, frequent recurrence, and poor prognosis of hepatocellular carcinoma (HCC) prompted us to identify new therapeutic targets or predictive markers of HCC diagnosis or prognosis. Methods. In this study, bioinformatics analysis was used to screen for target miRNAs from the open-access TCGA database. Transwell assays, Western blotting, and qRT-PCR analyses were used to detect cellular functions and gene expression in HCC cells and samples. A nude mouse tumorigenesis model was established to facilitate the observation of HCC progression. Other assays included luciferase reporter assays, IHC, and survival analysis. Results. We found that the identified miR-876 from TCGA was expressed at low levels in HCC cell lines and that low miR-876 expression was corrected with liver cirrhosis, tumor thrombus, and TNM stage. Further research revealed that miR-876 regulated cell invasion, EMT, and collagen expression by targeting POSTN expression. miR-876 and POSTN were inversely correlated in HCC samples and associated with EMT status and liver fibrosis in clinical HCC tissues. miR-876 inhibited the liver cancer progression in in vivo animal assays. Finally, both miR-876 and POSTN were risk factors for HCC survival, and HCC patients with combined low miR-876 and high POSTN expression had worse prognosis. Conclusions. miR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thus affecting HCC progression and prognosis. miR-876 and POSTN may be useful therapeutic targets or prognostic markers of HCC.

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“…140 The induction of EMT in HCC significantly promotes metastasis and is mediated by various molecular pathways including miRNAs, SSR2 and ID1. [141][142][143][144] Recent experiments have shed some light on the association between β-catenin signaling and EMT in HCC cells. The trans-activation response DNA-binding protein of 43 kDa (TDP-43) is suggested to suppress translation of GSK-3β to induce Wnt/β-catenin axis.…”

The Dysregulation of SOX Family Correlates with DNA Methylation and Immune Microenvironment Characteristics to Predict Prognosis in Hepatocellular Carcinoma

“…The co-expression molecules of SOX2 and SOX10 were really small, so the roles of these three SOX family molecules in HCC may need to be explored separately. In addition, the top 10 hub genes POSTN, BGN, MMP2, THBS2, CD34, ESR1, VEGFC, AEBP1, CLDN5, and LOXL1 seem to be related with cancer stemness (such as cancer-associated fibroblasts [ 55 ], EMT process [ 56 ], tumor immune infiltration [ 57 ], and metastasis [ 58 ]). In conclusion, the function of SOX family on HCC may link with these cancer stemness-related proteins, and these proteins may have a potential to be biomarkers or therapeutic targets.…”

Periostin: a predictable molecule to prognosis and chemotherapy responses of gastrointestinal and hepato-biliary-pancreatic malignant tumors?

“…MiR-876 inhibited HCC EMT and fibrosis by targeting POSTN, thereby affecting HCC progression and prognosis. MiR-876 and POSTN may be useful therapeutic targets or prognostic markers for HCC [47]. Another study demonstrated that the combined assessment of POSTN protein overexpression and microvascular invasion in HCC is associated with poor prognosis and can be used as a good prognostic marker for HCC [48].…”