MNS1 通过转位 β-catenin 激活 PI3K/AKT 促进肝癌发生和转移，并预测不良预后。

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

机构信息

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.

Endoscopy Center, Zhongshan Hospital, Fudan University, Shanghai, China.

出版信息

Liver Int. 2021 Jun;41(6):1409-1420. doi: 10.1111/liv.14803. Epub 2021 Feb 16.

DOI:10.1111/liv.14803

PMID:33506565

Abstract

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/γc(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 β-catenin. β-Catenin expression was crucial for MNS1's oncogenic effects. MNS1 indirectly translocated β-catenin from the cytoplasm to the nucleus via the MNS1-GSK3β 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.

摘要

背景与目的

肝细胞癌（HCC）是一种致命疾病，其特征是具有广泛的分子异质性。尽管肿瘤遗传学的重大进展导致了新的生物标志物的鉴定，但 HCC 患者的预后仍然不佳。

方法

采用定量逆转录聚合酶链反应（qRT-PCR）和 Western blot（WB）检测 HCC 细胞中减数分裂特异性核结构 1（MNS1）的表达。免疫组织化学染色检测 HCC 组织中 MNS1 的表达。通过 Cox 回归分析评估 MNS1 的临床意义。Transwell 检测评估细胞迁移能力。细胞计数试剂盒-8 和集落形成检测用于检测细胞增殖能力。采用 NOD/SCID/γc（null）（NOG）小鼠模型在体内研究 MNS1 的功能。

结果

MNS1 在大多数 HCC 组织中表达上调，与 HCC 患者的不良生存相关。功能实验揭示了 MNS1 的致癌作用，它通过 AKT 依赖性调节 β-连环蛋白促进 HCC 的生长和转移。β-连环蛋白的表达对 MNS1 的致癌作用至关重要。MNS1 通过 MNS1-GSK3β 轴将β-连环蛋白从细胞质间接转位到细胞核。