LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis.
LncRNA CDKN2BAS predicts poor prognosis in patients with hepatocellular carcinoma and promotes metastasis via the miR-153-5p/ARHGAP18 signaling axis.
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DOI：
10.18632/aging.101645
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发表时间：
2018-11-29
期刊：
影响因子：
--
通讯作者：
Teng L
中科院分区：
文献类型：
--
作者：
Chen J;Huang X;Wang W;Xie H;Li J;Hu Z;Zheng Z;Li H;Teng L
背景：越来越多的证据表明，长链非编码RNA（lncRNA）在癌症进展中起着至关重要的作用。然而，lncRNA CDKN2BAS是否参与人肝细胞癌（HCC）转移仍不清楚。方法：应用人类lncRNA基因芯片技术检测转移性肝癌组织中lncRNA的表达水平。采用MTT法、集落形成法、细胞迁移法、划痕法和流式细胞术检测CDKN2BAS对细胞增殖、迁移和凋亡的影响。异种移植实验用于证实CDKN2BAS对体内HCC的作用。进行qRT-PCR和Western印迹以确定mRNA和蛋白质的表达水平。荧光素酶报告基因分析用于鉴定特异性靶点关系。结果：CDKN2BAS在转移性肝癌组织中表达明显高于癌旁组织。CDKN2BAS在体外和体内促进HCC细胞生长和迁移。此外，CDKN2BAS通过海绵状microRNA-153 - 5p（miR-153 - 5p）上调Rho GT3活化蛋白18（ARHGAP 18）的表达，从而促进HCC细胞迁移。此外，CDKN 2BAS还下调Krüppel样因子13（KLF13）的表达，激活MEK-ERK1/2信号通路，从而减少肝癌细胞的凋亡。结论：lncRNA CDKN2BAS通过调控miR-153 - 5p/ARHGAP 18信号通路促进肝癌转移。
Background: Growing evidence shows that long noncoding RNAs (lncRNAs) play a crucial role in cancer progression. However, whether lncRNA CDKN2BAS is involved in human hepatocellular carcinoma (HCC) metastasis remains unclear. Methods: Human lncRNA microarray analysis was performed to detect differential expression levels of lncRNAs in metastatic HCC tissues. Effects of CDKN2BAS on cell proliferation, migration, and apoptosis were determined by MTT assay, colony formation assay, migration assay, scratch assay, and flow cytometry. The xenograft experiment was used to confirm the effect of CDKN2BAS on HCC in vivo. qRT-PCR and Western blot were performed to determine the expression levels of mRNAs and proteins. Luciferase reporter assay was used to identify the specific target relationships. Results: CDKN2BAS was remarkably up-regulated in metastatic HCC tissues compared with the adjacent non-tumor tissues. CDKN2BAS promotes HCC cell growth and migration in vitro and in vivo. Additionally, CDKN2BAS upregulated the expression of Rho GTPase activating protein 18 (ARHGAP18) by sponging microRNA-153-5p (miR-153-5p), and thus promoted HCC cell migration. Besides, CDKN2BAS downregulated the expression of Krüppel-like factor 13 (KLF13) and activated MEK-ERK1/2 signaling, thus reducing apoptosis in HCC cells. Conclusions: Our study revealed that lncRNA CDKN2BAS promotes HCC metastasis by regulating the miR-153-5p/ARHGAP18 signaling.
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影响因子：
--
作者：
Chow RKK;Tsz-Kwan Sin S;Liu M;Li Y;Man Chan TH;Song Y;Chen L;Lai-Wan Kwong D;Guan XY
通讯作者：
Guan XY
影响因子：
28.5
作者：
Huang MD;Chen WM;Qi FZ;Xia R;Sun M;Xu TP;Yin L;Zhang EB;De W;Shu YQ
通讯作者：
Shu YQ
影响因子：
37.3
作者：
Huang MD;Chen WM;Qi FZ;Sun M;Xu TP;Ma P;Shu YQ
通讯作者：
Shu YQ
影响因子：
11.2
作者：
Humphries, Brock;Wang, Zhishan;Yang, Chengfeng
通讯作者：
Yang, Chengfeng
影响因子：
8.8
作者：
Aleskandarany MA;Sonbul S;Surridge R;Mukherjee A;Caldas C;Diez-Rodriguez M;Ashankyty I;Albrahim KI;Elmouna AM;Aneja R;Martin SG;Ellis IO;Green AR;Rakha EA
通讯作者：
Rakha EA