MNS1 promotes hepatocarcinogenesis and metastasis via activating PI3K/AKT by translocating β-catenin and predicts poor prognosis

Background & Aims Hepatocellular carcinoma (HCC) is a fatal disease characterized by vast molecular heterogeneity. Although major advances in tumour genetics has led to the identification of new biomarkers, the prognosis of patients with HCC remains dismal. Methods Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were used to evaluate meiosis-specific nuclear structural 1 (MNS1) expression in HCC cells. Immunohistochemistry staining was used to evaluate MNS1 expression in HCC tissues. Clinical significance of MNS1 was evaluated by Cox regression analysis. Transwell assays were conducted to assess cells migration ability. Cell counting kit-8 and colony formation assays were performed to detect cells proliferation ability. NOD/SCID/gamma c(null) (NOG) mice model was adopted to investigate functions of MNS1 in vivo. Results The expression of MNS1, which is elevated in most HCC tissues, correlated with poor survival in HCC patients. Functional experiments revealed the oncogenic role of MNS1, which promotes HCC growth and metastasis through AKT-dependent modulation of beta-catenin. beta-Catenin expression was crucial for MNS1's oncogenic effects. MNS1 indirectly translocated beta-catenin from the cytoplasm to the nucleus via the MNS1-GSK3 beta axis. Conclusions MNS1 promotes HCC growth and metastasis via activating PI3K/AKT signalling and may serve as an important prognostic biomarker as well as potential novel therapeutic target for HCC.

Automated summary

This study found that MNS1 is highly expressed in HCC, correlated with poor patient survival, and promotes HCC growth and metastasis by activating the PI3K/AKT signaling pathway, as well as exerting oncogenic effects through modulation of beta-catenin.