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HOXA13 promotes colon cancer progression through β-catenin-dependent WNT pathway.
Experimental Cell Research ( IF 3.3 ) Pub Date : 2020-08-18 , DOI: 10.1016/j.yexcr.2020.112238
Yan Gu 1 , Jun Gu 1 , Kaicheng Shen 1 , Hongxu Zhou 1 , Jie Hao 1 , Fu Li 1 , Hua Yu 2 , Yueqi Chen 3 , Jianjun Li 1 , Yifei Li 1 , Houjie Liang 1 , Yan Dong 1
Affiliation  

Human class I homeobox A13 (HOXA13) was initially identified as a transcription factor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of HOXA13 in colon cancer development and progression are still unknown. In this study, we found that HOXA13 was highly expressed in colon cancer tissues, and its expression was associated with histological grade, T stage, N stage and tumour size. In vitro studies showed that HOXA13 promoted colon cancer cell proliferation, migration and invasion. Bioinformatics analysis revealed that HOXA13 expression was positively correlated with the WNT signalling pathway. In vitro studies showed that HOXA13 promoted the malignant phenotype of colon cancer cells by facilitating the nuclear translocation of β-Catenin. Moreover, XAV939, an inhibitor of β-Catenin, reversed the HOXA13-mediated effects on invasion and proliferation of colon cancer cells. In vivo studies further verified that HOXA13 promoted tumour formation through the Wnt/β-Catenin pathway. Collectively, these results suggest that HOXA13 is a potential oncogene that functions by promoting the nuclear translocation of β-Catenin, thereby maintaining the proliferation and metastasis of colon cancer.



中文翻译:

HOXA13通过β-catenin依赖性WNT途径促进结肠癌的进展。

人类I类同源盒A13(HOXA13)最初被确定为转录因子,在胚胎发育和恶性转化中具有重要作用。然而,HOXA13在结肠癌发展和进展中的临床意义和分子机制仍然未知。在这项研究中,我们发现HOXA13在结肠癌组织中高表达,并且其表达与组织学分级,T期,N期和肿瘤大小相关。体外研究表明,HOXA13促进结肠癌细胞的增殖,迁移和侵袭。生物信息学分析表明,HOXA13表达与WNT信号通路正相关。体外研究表明,HOXA13通过促进β-连环蛋白的核易位而促进了结肠癌细胞的恶性表型。此外,β-连环蛋白的抑制剂XAV939逆转了HOXA13介导的对结肠癌细胞侵袭和增殖的作用。体内研究进一步证实,HOXA13通过Wnt /β-Catenin途径促进肿瘤形成。总的来说,这些结果表明HOXA13是潜在的癌基因,其通过促进β-连环蛋白的核易位,从而维持结肠癌的增殖和转移而起作用。

更新日期:2020-08-21
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