Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells
| العنوان: | Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells |
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| المؤلفون: | Lopa Mishra, Bibhuti Mishra, Jian Chen, Jigisha Srivastav, Kazufumi Ohshiro |
| المصدر: | Genes & Cancer |
| بيانات النشر: | Impact Journals LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Mutation, HMGA2, biology, PJA1, hepatocellular carcinoma, HCCS, medicine.disease_cause, Ubiquitin ligase, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, GDF11, Genetics, biology.protein, Cancer research, medicine, TGF-β pathway, Signal transduction, ACVR1B, Transforming growth factor, Research Paper |
| الوصف: | Recently, we observed that the TGF-β pathway is altered in 39% of HCCs. The alterations are correlated with a raised HMGA2 level. Therefore, we compared genetic alterations of HMGA2 and 43 TGF-β pathway core genes in HCC patients from TCGA database. Genetic alterations of 15 genes, including INHBE, INHBC, GDF11, ACVRL and TGFB2 out of 43 core genes, highly-moderately matched that of HMGA2. Co-occurrences of mutation amplification, gains, deletions and high/low mRNA of HMGA2 with those of the core genes were highly significant in INHBE, INHBC, ACVR1B, ACVRL and GDF11. Mass spectrometry studies revealed that HMGA2 interacted with an E3 ligase, PJA1, and that this interaction is enhanced by TGF-β treatment in the nuclear of HCC cells. Co-localization of nuclear PJA1 and HMGA2 in HCC cells increased upon TGF-β treatment. Raised HMGA2 levels that occur with alterations in the TGF-β signaling pathway may reflect an altered activity of E3 ligases, such as PJA1, and potentially contribute to the tumor-promoting roles of TGF-β signaling. Here, we report that the co-occurrence of genetic alterations in HMGA2 and TGF-β pathway core genes is implicated in HCC progression, and propose that HMGA2 and PJA1 may be potential novel targets in dysfunctional TGF-β signaling in HCC. |
| اللغة: | English |
| تدمد: | 1947-6027 1947-6019 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e7f9492ad40bb47f4baddeaf5ca59b34 http://europepmc.org/articles/PMC7289907 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e7f9492ad40bb47f4baddeaf5ca59b34 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19476027 19476019 |
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