Dataset Information

HMGA1 stimulates MYH9-dependent ubiquitination of GSK-3β via PI3K/Akt/c-Jun signaling to promote malignant progression and chemoresistance in gliomas.

ABSTRACT: Myosin heavy chain 9 (MYH9) plays an essential role in human diseases, including multiple cancers; however, little is known about its role in gliomas. In the present study, we revealed that HMGA1 and MYH9 were upregulated in gliomas and their expression correlated with WHO grade, and HMGA1 promoted the acquisition of malignant phenotypes and chemoresistance of glioma cells by regulating the expression of MYH9 through c-Jun-mediated transcription. Moreover, MYH9 interacted with GSK-3β to inhibit the expression of GSK-3β protein by promoting its ubiquitination; the downregulation of GSK-3β subsequently promoted the nuclear translocation of β-catenin, enhancing growth, invasion, migration, and temozolomide resistance in glioma cells. Expression levels of HMGA1 and MYH9 were significantly correlated with patient survival and should be considered as independent prognostic factors. Our findings provide new insights into the role of HMGA1 and MYH9 in gliomagenesis and suggest the potential application of HMGA1 and MYH9 in cancer therapy in the future.

SUBMITTER: Que T

PROVIDER: S-EPMC8660812 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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HMGA1 stimulates MYH9-dependent ubiquitination of GSK-3β via PI3K/Akt/c-Jun signaling to promote malignant progression and chemoresistance in gliomas.

Que Tianshi T Zheng Haojie H Zeng Yu Y Liu Xinru X Qi Ge G La Qingcuo Q Liang Tuo T Li Zhiyong Z Yi Guozhong G Zhang Shichao S Li Junjie J Nie Jing J Tan Jian-Er JE Huang Guanglong G

Cell death & disease 20211210 12

Myosin heavy chain 9 (MYH9) plays an essential role in human diseases, including multiple cancers; however, little is known about its role in gliomas. In the present study, we revealed that HMGA1 and MYH9 were upregulated in gliomas and their expression correlated with WHO grade, and HMGA1 promoted the acquisition of malignant phenotypes and chemoresistance of glioma cells by regulating the expression of MYH9 through c-Jun-mediated transcription. Moreover, MYH9 interacted with GSK-3β to inhibit ...[more]

PMID: 34887392

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Project description:BackgroundAbnormal expression of Fanconi anaemia complementation group I (FANCI) has been implicated in carcinogenesis. However, the precise role of FANCI in the development of hepatocellular carcinoma (HCC) remains unclear.Materials & methodsWe conducted a comprehensive bioinformatics analysis of FANCI's role based on HCC patient sequencing data in the TCGA and GEO databases. Then, we performed qPCR, Western blotting (WB), and immunohistochemistry (IHC) assays. SiRNA-mediated knockdown of FANCI was conducted, followed by CCK-8, EdU staining, and colony formation experiments to evaluate the impact of FANCI knockdown on HCC cell behaviour. Flow cytometry was employed to explore alterations in the cell cycle after FANCI knockdown in HCC cell lines. Furthermore, RNA sequencing was performed to investigate potential mechanisms following FANCI knockdown, and WB analysis was used to validate the corresponding pathway.ResultsOur bioinformatics analysis revealed elevated expression of FANCI in HCC, which was subsequently validated through qPCR, WB, and IHC assays. High expression of FANCI was significantly associated with a poor prognosis in HCC patients. Univariate and multivariate Cox regression analyses identified FANCI as an independent prognostic risk factor for HCC patients. Additionally, the coexpressed genes of FANCI were found to be associated with multiple cancer pathways. Knockdown of FANCI expression significantly inhibited HCC cell proliferation and colony formation by inducing cell cycle arrest. Further WB analysis revealed that FANCI knockdown suppressed the expression of Cyclin D1 and p-AKT while increasing the expression of GSK-3β in HCC cells. However, no significant differences were observed in the expression levels of AKT and PI3K.ConclusionOverall, our research provides substantial proof of FANCI's crucial function as an oncogene in HCC. It could serve as a potential prognostic marker, therapeutic target, and tumorigenic factor in HCC.

Dataset Information

HMGA1 stimulates MYH9-dependent ubiquitination of GSK-3β via PI3K/Akt/c-Jun signaling to promote malignant progression and chemoresistance in gliomas.

Publications

HMGA1 stimulates MYH9-dependent ubiquitination of GSK-3β via PI3K/Akt/c-Jun signaling to promote malignant progression and chemoresistance in gliomas.

Similar Datasets

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