Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia
Loss of androgen receptor promotes HCC invasion and metastasis via activating circ-LNPEP/miR-532-3p/RAB9A signal under hypoxia
复制标题
雄激素受体的缺失通过缺氧下激活circ-LNPEP/miR-532-3p/RAB9A信号促进HCC侵袭和转移。
DOI：
10.1016/j.bbrc.2021.02.120
复制
发表时间：
2021-04-13
影响因子：
3.1
通讯作者：
Xiao, Yao
中科院分区：
文献类型：
--
作者：
Ouyang, Xiwu;Yao, Lei;Xiao, Yao
开发新的靶向治疗仍然是肝细胞癌（HCC）治疗的优先事项。早期的研究表明雄激素受体（AR）在HCC的进展中起抑制作用。然而，AR抑制肝癌发展的潜在机制仍然难以捉摸，特别是在缺氧条件下。在此，我们证明AR/circ-LNPEP/miR-532- 3 p/RAB 9A信号传导轴与低氧诱导的HCC细胞侵袭密切相关。AR作为转录因子降低circ-LNPEP表达水平，释放其对miR 532 - 3 p的海绵作用，导致RAB 9A表达下调，抑制肝癌细胞的侵袭。体外和体内动物模型也证实，过表达circ-LNPEP可逆转AR对HCC细胞侵袭或肿瘤转移的抑制作用。总的来说，我们的研究补充了AR在缺氧条件下抑制HCC侵袭/转移的关键机制，为开发更好治疗HCC的新疗法提供了令人信服的理由。(c)2021爱思唯尔公司All rights reserved.
Development of novel targeted therapies remains the priority in hepatocellular carcinoma (HCC) treatments. Early reports have demonstrated that androgen receptor (AR) plays a suppressive role in HCC progression. However, the underlying mechanisms by which AR attenuates HCC development are still elusive, especially under hypoxic conditions. Herein, we demonstrated that AR/circ-LNPEP/miR-532-3p/ RAB9A signaling axis was tightly involved in hypoxia-induced cell invasion of HCC cells. AR worked as a transcription factor to reduce circ-LNPEP expression level, which released its sponge potential of miR532-3p, leading to the downregulation of RAB9A and inhibiting cell invasion of HCC cells. In vitro and in vivo animal model also confirmed that overexpression of circ-LNPEP could reverse the suppressive effect of AR on HCC cell invasion or tumor metastasis. Overall, our study supplements a critical mechanism by which AR suppresses HCC invasion/metastasis under hypoxic conditions, providing compelling rationale to develop novel therapy for better treatments of HCC. (c) 2021 Elsevier Inc. All rights reserved.