HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer.

HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer.
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DOI:
10.18632/aging.103824
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发表时间:
2020-09-07
期刊:
Aging
影响因子:
--
通讯作者:
Yin G
Yin G
中科院分区:
其他
文献类型:
--
作者:
Peng Y;Li Y;Li Y;Wu A;Fan L;Huang W;Fu C;Deng Z;Wang K;Zhang Y;Shu G;Yin G

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卵巢癌的死亡率是妇科癌症中最高的,主要是由于转移症状。最近的研究表明,HOX基因在肿瘤进展中至关重要,但其潜在机制仍不清楚。在此,在卵巢癌组织中检测HOXC 10表达。通过体外和体内腹腔注射研究HOXC 10在卵巢癌转移中的作用。共有158名有足够记录的卵巢癌患者入选分析。HOXC 10与卵巢癌的转移和不良预后相关。在体外,HOXC 10过表达促进卵巢癌细胞迁移。此外,HOXC 10正调控Slug表达,改变癌细胞的迁移能力。此外,我们的研究表明miR-222- 3 p是HOXC 10的抑制因子。在体内,在注射miR-222- 3 p agomir(一种过表达试剂)后,在具有稳定HOXC 10过表达的肿瘤的异种移植小鼠中观察到肝转移减少。本研究首次证明HOXC 10通过调节EMT相关基因Slug的转录促进卵巢癌转移。此外,我们发现HOXC 10受miR-222- 3 p的调控。这些数据突出了HOXC 10在增强卵巢癌转移中的关键作用,并可能为卵巢癌提供治疗靶点。
The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated in vitroand via intraperitoneal injection in vivo. A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. In vitro, HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. In vivo, a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.
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