Abstract
α-Actinin1 (ACTN1), an actin cross-linking protein, is implicated in cytokinesis, cell adhesion, and cell migration. In addition, it is involved in the tumorigenesis and development of certain cancers, such as breast cancer. We explored the function of ACTN1 in gastric cancer (GC), which has largely remained unclear. High-throughput sequencing and public microarray datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) revealed the upregulation of ACTN1 in gastric cancer with a poor prognosis. These results were further verified by western blotting (WB), Real-Time Quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry. We constructed loss and gain of function gastric cancer cells, which revealed the effect of ACTN1 over-expression on promoting GC cell proliferation, invasion, migration, and inhibited apoptosis. Mechanistic studies revealed that ACTN1 regulates the epithelial-mesenchymal transition (EMT) and tumorigenesis of gastric cancer via the AKT/GSK3β/β-catenin pathway, confirmed by the inhibitor of AKT MK2206. Altogether, these results demonstrated that ACTN1 could be a promising candidate for gastric cancer treatment.
Keywords:
AKT/GSK3Β/β-catenin; Gastric cancer; apoptosis; epithelial-to-mesenchymal transition; α-Actinin1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actinin* / genetics
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Actinin* / metabolism
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Aged
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Apoptosis / genetics
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Carcinogenesis / genetics
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Cell Line, Tumor
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Epithelial-Mesenchymal Transition / genetics*
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Female
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Glycogen Synthase Kinase 3 beta / genetics
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Glycogen Synthase Kinase 3 beta / metabolism
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Humans
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Male
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Middle Aged
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / genetics
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Stomach Neoplasms* / genetics
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Stomach Neoplasms* / metabolism
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Stomach Neoplasms* / mortality
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Stomach Neoplasms* / pathology
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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ACTN1 protein, human
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CTNNB1 protein, human
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beta Catenin
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Actinin
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Proto-Oncogene Proteins c-akt
Grants and funding
This work was supported by the National Natural Science Foundation of China[grant no. 82060430],the Provincial Key Laboratory Cultivation Project of Guangxi Region [grant no.YYZS2020003], the Guangxi Science and Technology Project [grant no.[2019] 367; grant no.AD19245196], the Guangxi University Innovation Team and Outstanding Scholar Project [grant no.[2018] 35], the Guangxi Key Research and Development Project [grant no.AB18126058] and the Guangxi Graduate Education Innovation Project [grant no.YCBZ2019043];