Transforming growth factor-β-activated kinase 1 (TAK1)-binding protein 3 (TAB3) and the proviral integration site for Moloney murine leukaemia virus 1 (PIM1) are implicated in cancer development. In this study, we investigated the relationship between TAB3 and PIM1 in colorectal cancer (CRC) and determined the potential role and molecular mechanism of TAB3 in PIM1-mediated CRC growth. We found that TAB3 and PIM1 expression levels were positively correlated in CRC tissues. The knockdown of TAB3 significantly decreased PIM1 expression and inhibited CRC proliferation in vitro and in vivo. The upregulation of PIM1 rescued the decreased cell proliferation induced by TAB3 knockdown, whereas PIM1 knockdown decreased TAB3-enhanced CRC proliferation. Additionally, TAB3 regulates PIM1 expression through the STAT3 signalling pathway and confirmed a positive correlation between TAB3 and phosphorylated-STAT3 expression in CRC tissues. Patients with high expression of TAB3 and phosphorylated-STAT3 had the worst prognosis. Mechanistically, TAB3 regulates PIM1 expression by promoting STAT3 phosphorylation and activation through the formation of the TAB3-TAK1-STAT3 complex. Overall, a novel CRC regulatory circuit involving the TAB3-TAK1-STAT3 complex and PIM1 was identified, the dysfunction of which may contribute to CRC tumorigenesis.

中文翻译：

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TAB3通过直接激活TAK1-STAT3复合物以促进结直肠癌的生长来上调PIM1表达。

转化生长因子-β激活的激酶1（TAK1）结合蛋白3（TAB3）和莫洛尼氏鼠白血病病毒1（PIM1）的前病毒整合位点与癌症发展有关。在这项研究中，我们调查了TAB3和PIM1在结直肠癌（CRC）中的关系，并确定了TAB3在PIM1介导的CRC生长中的潜在作用和分子机制。我们发现在CRC组织中TAB3和PIM1表达水平呈正相关。敲低TAB3显着降低PIM1表达，并在体外和体内抑制CRC增殖。PIM1的上调挽救了由TAB3敲低诱导的细胞增殖减少，而PIM1的敲低则减少了TAB3增强的CRC增殖。另外，TAB3通过STAT3信号通路调节PIM1表达，并证实CRC组织中TAB3与磷酸化STAT3表达呈正相关。TAB3和磷酸化STAT3高表达的患者预后最差。从机理上讲，TAB3通过促进STAT3的磷酸化和TAB3-TAK1-STAT3复合物的激活来调节PIM1的表达。总体而言，已鉴定出涉及TAB3-TAK1-STAT3复合物和PIM1的新型CRC调节回路，其功能障碍可能有助于CRC肿瘤发生。TAB3通过促进STAT3的磷酸化和TAB3-TAK1-STAT3复合物的激活来调节PIM1的表达。总体而言，已鉴定出涉及TAB3-TAK1-STAT3复合物和PIM1的新型CRC调节回路，其功能障碍可能有助于CRC肿瘤发生。TAB3通过促进STAT3磷酸化和TAB3-TAK1-STAT3复合物的激活来调节PIM1表达。总体而言，已鉴定出涉及TAB3-TAK1-STAT3复合物和PIM1的新型CRC调节回路，其功能障碍可能有助于CRC肿瘤发生。