FGD1 exhibits oncogenic properties in hepatocellular carcinoma through regulating cell morphology, autophagy and mitochondrial function
FGD1 exhibits oncogenic properties in hepatocellular carcinoma through regulating cell morphology, autophagy and mitochondrial function
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FGD1 通过调节细胞形态、自噬和线粒体功能在肝细胞癌中表现出致癌特性
DOI：
10.1016/j.biopha.2020.110029
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发表时间：
2020
影响因子：
7.5
通讯作者：
Songqing He
中科院分区：
文献类型：
--
作者：
Yonglian Zeng;Zhenya Guo;Zhigao Hu;Mingjiang Liu;Yubing Chen;Shilian Chen;Bo Peng;Peng Zhang;Zhan Wu;Hongliang Luo;Fudi Zhong;Keqing Jiang;Yi Lu;Gu;ou Yuan;Songqing He
面生殖发育不良1（FGD 1）参与了多种生物学过程，包括细胞骨架重构、细胞形态、细胞周期进程和细胞极性。FGD 1的异常表达也在几种类型的癌症中被鉴定，表明其在癌症发展中的关键作用。然而，FGD 1在肝细胞癌（HCC）中的作用知之甚少。在这项研究中，FGD 1在HCC中的表达与癌症基因组图谱的RNA测序数据挖掘。通过过表达或敲低FGD 1，在体外和体内研究FGD 1对肝癌恶性行为的影响。我们发现FGD 1在HCC中表达上调，并与HCC的发展和预后相关。通过过表达或敲低FGD 1，在体外和体内研究FGD 1对肝癌恶性行为的影响。FGD1的敲除可显着抑制肝癌细胞的恶性行为，并导致肝癌细胞伪足形态异常、自噬抑制和线粒体功能障碍。进一步的研究表明，Cdc42，一个Rho GTdR，在这些过程中发挥作用。FGD 1的过表达显著促进HCC细胞的致癌特性。总的来说，这些发现揭示了FGD 1通过调节细胞形态、自噬和线粒体功能在HCC中表现出致癌特性，表明FGD 1可能作为HCC的潜在治疗靶点。
Faciogenital Dysplasia 1 (FGD1) has been involved in a variety of biological processes, including cytoskeleton restructuring, cell morphology, cell cycle progression, and cell polarity. Abnormal expression of FGD1 was also identified in several types of cancers, indicating its critical role in the development of cancers. However, little is known about the role of FGD1 in hepatocellular carcinoma (HCC). In this study, the expression of FGD1 in HCC was mined with the RNA sequencing data from the cancer genome atlas. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. We find that FGD1 is up-regulated in HCC and correlated with the development and prognosis of HCC. By over-expressing or knocking down of FGD1, the effects of FGD1 on the malignant behavior of HCC were evaluated both in vitro and in vivo. Knockdown of FGD1 remarkably inhibits the malignant behaviors and causes morphological disorder of pseudopodia, autophagy inhibition and mitochondrial dyfunction in HCC cells. Further investigation shows that Cdc42, a Rho GTPase, plays a role in these processes. Overexpression of FGD1 significantly promotes the oncogenic properties of HCC cells. Collectively, these findings reveal that FGD1 exhibits oncogenic properties in HCC through regulating cell morphology, autophagy and mitochondrial function, suggesting that FGD1 may serve as a potential therapeutic target for HCC.