miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition.
miR-139-5p Loss-Mediated WTAP Activation Contributes to Hepatocellular Carcinoma Progression by Promoting the Epithelial to Mesenchymal Transition.
复制标题
DOI：
10.3389/fonc.2021.611544
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Song W
中科院分区：
文献类型：
--
作者：
Liu W;Gao X;Chen X;Zhao N;Sun Y;Zou Y;Guan Y;Yang L;Pei X;Wang G;Wang B;Li M;Song W
背景：肝细胞癌（HCC）是一种原发性侵袭性胃肠道肿瘤，影响世界各地的患者。已经表明，Wilms肿瘤1相关蛋白（WTAP）在各种癌症中经常上调。然而，WTAP在HCC中的潜在作用在很大程度上仍然未知。方法：采用免疫印迹法和免疫组化法检测WTAP在人肝癌组织中的表达。分析WTAP表达与临床病理特征及肝癌预后的相关性。采用短发夹RNA（shRNA）沉默WTAP基因表达，观察WTAP基因沉默对肝癌细胞增殖和侵袭能力的影响。通过生物信息学分析鉴定了参与WTAP表达调控的microRNA（miRNAs），并通过体外试验进一步证实。结果如下：WTAP在肝癌组织中的表达水平显著高于癌旁正常组织，且与肝癌患者的临床分期和预后显著相关。进一步的研究表明，WTAP基因的敲低显著抑制了肝癌细胞的增殖和侵袭能力。荧光素酶报告基因测定和验证实验证实WTAP是miR-139- 5 p的直接靶点。WTAP的过表达可部分消除miR-139- 5 p对肝癌细胞生长和侵袭的抑制作用。从机制上讲，我们揭示了miR-139- 5 p/WTAP轴通过控制上皮向间质转化（EMT）来调节HCC的进展。结论：WTAP是HCC中潜在的癌基因，miR-139- 5 p负调控WTAP的表达。miR-139- 5 p/WTAP可作为HCC的潜在治疗靶点。
Background: Hepatocellular carcinoma (HCC) is a primary aggressive gastrointestinal neoplasm that affects patients worldwide. It has been shown that Wilms' tumor 1-associating protein (WTAP) is frequently upregulated in various cancers. However, the potential role of WTAP in HCC remains largely unknown. Methods: The expression levels of WTAP in human HCC tissues were determined by the western blotting and immunohistochemical (IHC) staining. A correlation between the WTAP expression, clinicopathological features, and the HCC prognosis was analyzed. The WTAP expression was silenced by short hairpin RNA (shRNA), and effects of the knockdown of WTAP on the proliferation and invasion of HCC cells were assessed. The microRNAs (miRNAs) involved in the regulation of the WTAP expression were identified by a bioinformatics analysis and further confirmed by in vitro assays. Results: The expression levels of WTAP in liver cancer tissues were significantly elevated and compared with those in the adjacent normal tissues and significantly correlated with the clinical stage and prognosis in patients with HCC. Further investigation revealed that the knockdown of WTAP drastically suppressed HCC cell proliferation and invasion abilities. Luciferase reporter assay and validation experiments confirmed that WTAP was a direct target of miR-139-5p. Moreover, the overexpression of WTAP could partly abolish the inhibitory effects of miR-139-5p on the HCC cell growth and invasion. Mechanistically, we revealed that the miR-139-5p/WTAP axis regulated the HCC progression by controlling the epithelial to mesenchymal transition (EMT). Conclusions: In summary, the results indicate that WTAP is a potential oncogene in HCC and miR-139-5p negatively regulates the WTAP expression. MiR-139-5p/WTAP can be utilized as a potential therapeutic target for HCC.
登录
查看更多内容
DOI：
10.1186/s13046-018-0706-6
发表时间：
2018-02-27
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Tang J;Wang F;Cheng G;Si S;Sun X;Han J;Yu H;Zhang W;Lv Q;Wei JF;Yang H
通讯作者：
Yang H
影响因子：
12.4
作者：
Dai X;Guo Y;Hu Y;Bao X;Zhu X;Fu Q;Zhang H;Tong Z;Liu L;Zheng Y;Zhao P;Fang W
通讯作者：
Fang W
影响因子：
3.5
作者：
Little, NA;Hastie, ND;Davies, RC
通讯作者：
Davies, RC
影响因子：
2.6
作者：
Macfarlane LA;Murphy PR
通讯作者：
Murphy PR
M6A RNA 甲基化调节因子 HNRNPC 有助于多形性胶质母细胞瘤的肿瘤发生并预测预后
影响因子：
4.7
作者：
Wang LC;Chen SH;Shen XL;Li DC;Liu HY;Ji YL;Li M;Yu K;Yang H;Chen JJ;Qin CZ;Luo MM;Lin QX;Lv QL
通讯作者：
Lv QL