HOXA13 promotes colon cancer progression through β-catenin-dependent WNT pathway
HOXA13 promotes colon cancer progression through β-catenin-dependent WNT pathway
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HOXA13通过β-连环蛋白依赖性WNT途径促进结肠癌进展
DOI：
10.1016/j.yexcr.2020.112238
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发表时间：
2020-10-15
影响因子：
3.7
通讯作者：
Dong, Yan
中科院分区：
文献类型：
--
作者：
Gu, Yan;Gu, Jun;Dong, Yan
人类I类同源盒A13(HOXA13)最初被鉴定为一种转录因子，在胚胎发育和恶性转化中起重要作用。然而，HOXA13在结肠癌发生发展中的临床意义和分子机制尚不清楚。在本研究中，我们发现HOXA13在结肠癌组织中高表达，其表达与组织学分级、T分期、N分期和肿瘤大小有关。体外研究表明，HOXA13可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的表达与WNT信号通路呈正相关。体外研究表明，HOXA13通过促进β-连环蛋白的核转位促进结肠癌细胞的恶性表型。此外，β-连环素的抑制剂XAV939逆转了HOXA13对结肠癌细胞侵袭和增殖的影响。体内研究进一步证实，HOXA13通过Wnt/β-catenin途径促进肿瘤形成。综上所述，这些结果表明HOXA13是一个潜在的癌基因，它通过促进β-连环蛋白的核转位发挥作用，从而维持结肠癌的增殖和转移。
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 beta-Catenin. Moreover, XAV939, an inhibitor of beta-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/beta-Catenin pathway. Collectively, these results suggest that HOXA13 is a potential oncogene that functions by promoting the nuclear translocation of beta-Catenin, thereby maintaining the proliferation and metastasis of colon cancer.