在HCC细胞中,TGF-β信号的改变可能通过调节PJA1/SMAD3导致HMGA2水平升高。

Q2 Biochemistry, Genetics and Molecular Biology
Kazufumi Ohshiro, Jian Chen, Jigisha Srivastav, Lopa Mishra, Bibhuti Mishra
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引用次数: 6

摘要

最近,我们观察到TGF-β通路在39%的hcc中发生改变。这些变化与HMGA2水平升高有关。因此,我们比较了TCGA数据库中HCC患者HMGA2和43个TGF-β通路核心基因的遗传改变。43个核心基因中,INHBE、INHBC、GDF11、ACVRL、TGFB2等15个基因的遗传改变与HMGA2高度中等匹配。在INHBE、INHBC、ACVR1B、ACVRL和GDF11中,HMGA2与核心基因的突变扩增、获得、缺失和高/低mRNA共现均高度显著。质谱研究显示HMGA2与E3连接酶PJA1相互作用,并且这种相互作用在HCC细胞核中通过TGF-β处理而增强。TGF-β处理HCC细胞后,核PJA1和HMGA2共定位增加。随着TGF-β信号通路的改变,HMGA2水平升高可能反映了E3连接酶(如PJA1)活性的改变,并可能有助于TGF-β信号通路的促肿瘤作用。在这里,我们报道了HMGA2和TGF-β通路核心基因基因改变的共同发生与HCC进展有关,并提出HMGA2和PJA1可能是HCC中功能失调的TGF-β信号传导的潜在新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells.

Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells.

Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells.

Alterations in TGF-β signaling leads to high HMGA2 levels potentially through modulation of PJA1/SMAD3 in HCC cells.

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.

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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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