Dataset Information

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma.

ABSTRACT:

Background

PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC.

Methods

PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing.

Results

PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2.

Conclusions

This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

SUBMITTER: Zhao J

PROVIDER: S-EPMC7885213 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma.

Zhao JiangSheng J Chen GuoFeng G Li Jingqi J Liu Shiqi S Jin Quan Q Zhang ZhengWei Z Qi Fuzhen F Zhang JianHuai J Xu JianBo J

Cancer cell international 20210215 1

<h4>Background</h4>PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC.<h4>Methods</h4>PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. ...[more]

PMID: 33588847

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Project description:Hepatocellular carcinoma (HCC) is a malignant tumor with a high metastatic rate. Recent studies have shown that the mitosis‑associated spindle‑assembly checkpoint regulatory protein spindle pole body component 25 homolog (SPC25) promotes HCC progression, although the underlying mechanism has yet to be fully elucidated. The aim of the present study was to investigate the mechanism through which SPC25 may promote HCC progression in greater detail. First, the expression of SPC25 was analyzed in publicly available databases to explore the association between SPC25 and HCC metastasis. Western blotting was subsequently performed to examine the level of SPC25 expression in different HCC cell lines. SPC25 was then silenced in HCCLM3 and Huh7 cells, and the effects of SPC25 silencing were investigated using cell proliferation, wound‑healing, Transwell migration assays and an in vivo mouse model. Finally, the mechanism of SPC25 action with respect to the promotion of HCC metastasis was explored using microarray analysis and rescue experiments. The results obtained demonstrated that SPC25 is highly expressed in HCC, and this high level of expression is associated with poor prognosis and metastasis. Moreover, SPC25 silencing led to a marked inhibition of the invasion and migration of HCC cells both in vitro and in vivo. The gene‑expression profiling and mechanistic experiments suggest that SPC25 preferentially influences the expression of genes associated with extracellular matrix (ECM)‑integrin interactions, including integrin subunit β4 (ITGB4), an upstream element of the integrin pathway. ITGB4 upregulation partly reversed the decline in cell invasion and migration capacities that resulted from SPC25 silencing. Furthermore, deleting both SPC25 and ITGB4 caused a decrease in the phosphorylation of focal adhesion kinase (FAK), phosphoinositide 3‑kinase (PI3K) and AKT, which are downstream elements of the integrin pathway. Taken together, the results of the present study demonstrated the important role of SPC25 as a prognostic indicator and as a promoter of metastasis in HCC, and the underlying mechanism of its action has been partially elucidated, suggesting that SPC25 could be used as a biomarker and as a target for therapeutic intervention in the treatment of HCC.

Dataset Information

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma.

Similar Datasets

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