Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.
Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.
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环状RNA hsa_circ_0003288通过调控hsa_circ_0003288/miR-145/PD-L1轴诱导肝癌EMT和侵袭
DOI：
10.1186/s12935-021-01902-2
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发表时间：
2021-04-15
影响因子：
5.8
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Xu G;Zhang P;Liang H;Xu Y;Shen J;Wang W;Li M;Huang J;Ni C;Zhang X;Zhu X
上皮-间质转化（EMT）与伤口愈合、肿瘤发生和转移有关。Circular RNA（circRNA）是一类参与多种人类癌症的功能性非编码RNA。然而，circRNA是否以及如何有助于肝细胞癌（HCC）中的EMT仍有待破译。在这项研究中，我们研究了hsa_circ_0003288在EMT和HCC侵袭过程中对程序性死亡1配体1（PD-L1）的调节和功能。通过实时定量逆转录酶PCR（qRT-PCR）测量Hsa_circ_0003288表达。使用荧光素酶报告基因测定、RNA下拉测定和荧光原位杂交（FISH）来确定hsa_circ_0003288与miR-145之间以及miR-145与PD-L1之间的相关性。此外，hsa_circ_0003288的异位过表达和siRNA介导的下调、transwell测定和体内研究用于确定hsa_circ_0003288对L02和HCC细胞的EMT和侵袭力的功能。miR-145直接靶向PD-L1 3′-非翻译区（UTR）区域，hsa_circ_0003288作为miR-145海绵调控PD-L1表达。hsa_circ_0003288的过表达增加了PD-L1水平，并促进了L02细胞的EMT、迁移和侵袭。在HepG 2和Huh 7细胞中敲低hsa_circ_0003288后，这些观察结果被逆转。PD-L1的过表达挽救了hsa_circ_0003288敲低后HepG 2和Huh 7细胞的EMT、迁移和侵袭性。此外，在体内研究中，hsa_circ_0003288敲低降低了EMT。发现Hsa_circ_0003288/PD-L1轴通过PI 3 K/Akt通路介导HCC的转移表型。此外，HCC组织中hsa_circ_0003288的表达水平升高，并与PD-L1表达呈正相关。我们的研究结果表明，hsa_circ_0003288通过PI 3 K/Akt途径，通过hsa_circ_0003288/miR-145/PD-L1轴促进HCC的EMT和侵袭。靶向hsa_circ_0003288可能是治疗HCC的治疗策略。
Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. miR-145 directly targeted the PD-L1 3′-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.
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影响因子：
--
作者：
Ock CY;Kim S;Keam B;Kim M;Kim TM;Kim JH;Jeon YK;Lee JS;Kwon SK;Hah JH;Kwon TK;Kim DW;Wu HG;Sung MW;Heo DS
通讯作者：
Heo DS
影响因子：
4.6
作者：
Li C;Lu L;Feng B;Zhang K;Han S;Hou D;Chen L;Chu X;Wang R
通讯作者：
Wang R
EMT，癌症干细胞和耐药性：癌症战争中新兴的邪恶轴。
影响因子：
8
作者：
Singh, A.;Settleman, J.
通讯作者：
Settleman, J.
影响因子：
--
作者：
Fu L;Chen Q;Yao T;Li T;Ying S;Hu Y;Guo J
通讯作者：
Guo J
影响因子：
13.5
作者：
Han, Dan;Li, Jiangxue;Cao, Xuetao
通讯作者：
Cao, Xuetao