TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways.

TRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways.
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TRIM14通过PTEN/PI3K/AKT和STAT3途径调节黑色素瘤恶性肿瘤。

DOI:
10.18632/aging.203003
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发表时间:
2021-05-11
期刊:
Aging
影响因子:
--
通讯作者:
Xiang D
Xiang D
中科院分区:
其他
文献类型:
--
作者:
Chen J;Huang L;Quan J;Xiang D

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黑色素瘤是最具侵袭性的癌症之一,总体存活率很低。到目前为止,治疗黑色素瘤的有效方法仍然很少。TRIM14是一种重要的癌基因,与多种肿瘤有关。然而,TRIM14在黑色素瘤中的作用仍不清楚。在这项研究中,我们发现TRIM14在黑色素瘤细胞系中异常上调。TRIM14基因敲除可抑制黑色素瘤细胞的增殖、迁移、侵袭、上皮间充质转化和黑色素合成。TRIM14的过表达对黑色素瘤细胞系的细胞功能有相反的影响。进一步的研究表明,TRIM14基因敲除增加了PTEN蛋白水平,进而使AKT和STAT3通路失活。此外,用特定的抑制剂阻断AKT或STAT3通路可以部分逆转TRIM14过表达对黑色素瘤恶性程度的促进作用。此外,体内试验也支持上述发现。这些结果表明,TRIM14可能是治疗黑色素瘤的一个有前途的靶点。
Melanoma is one of the most aggressive cancers with poor overall survival. To date, there are still few effective methods for the treatment of melanoma. TRIM14 was previously reported to be an important oncogene in many tumors. Nevertheless, the roles of TRIM14 in melanoma remain unknown. In this study, we found that TRIM14 was abnormally upregulated in melanoma cell lines. Knockdown of TRIM14 suppressed melanoma cell proliferation, migration, invasion, epithelial-mesenchymal transition, and melanin synthesis. Overexpression of TRIM14 had opposite effects on the cellular functions of melanoma cell lines. Further study revealed that TRIM14 knockdown increased PTEN protein levels, which in turn inactivated AKT and STAT3 pathways. Moreover, blocking AKT or STAT3 pathway with a specific inhibitor could partially reverse the promotion of melanoma malignancy mediated by TRIM14 overexpression. In addition, in vivo assay also supported the above findings. These results indicated that TRIM14 might be a promising target for melanoma treatment.
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