Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.
Predicting Value of ALCAM as a Target Gene of microRNA-483-5p in Patients with Early Recurrence in Hepatocellular Carcinoma.
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ALCAM作为microRNA-483-5p靶基因对肝细胞癌早期复发的预测价值
DOI：
10.3389/fphar.2017.00973
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发表时间：
2017
影响因子：
5.6
通讯作者：
Cong WM
中科院分区：
文献类型：
--
作者：
Lu XY;Chen D;Gu XY;Ding J;Zhao YJ;Zhao Q;Yao M;Chen Z;He XH;Cong WM
肝细胞癌（HCC）的长期生存率较低。生存率低的原因之一是肝内转移引起的高复发率，这对长期预后有不利影响。许多研究表明microRNAs在HCC中发挥重要作用，但尚未有通过分析microRNAs来研究复发性HCC （RHCC）克隆起源的研究。在本研究中，我们通过miRNA芯片筛选发现miR-483-5p在短期复发（≤2年）的RHCC组织中显著上调，在体外可显著促进HCC细胞的迁移和侵袭，在体内可显著增加裸鼠肝内转移。此外，我们发现活化的白细胞粘附分子（activated leukocyte cell adhesion molecule， ALCAM）是miR-483-5p的直接靶点，它能显著抑制HCC细胞的迁移和侵袭，重新引入ALCAM表达可以拮抗miR-483-5p对HCC细胞迁移和侵袭能力的促进作用。此外，ALCAM的表达水平与微血管侵袭和肿瘤大小呈负相关，被认为是预后因素。ALCAM阴性患者的复发时间比阳性患者短，单因素和多因素生存分析显示ALCAM是HCC复发的独立危险因素。qRT-PCR和Western blotting结果显示，干扰或过表达ALCAM后，EMT相关基因（MMP-2、MMP-9、E-caherin、vimentin）的表达发生显著变化，且ALCAM与EMT在HCC中存在显著相关性。这些结果表明，miR-483-5p/ALCAM轴是HCC侵袭转移的重要调节因子和复发风险评估的生物标志物。
The long-term survival rate of hepatocellular carcinoma (HCC) is poor. One of the reasons for the poor rate of survival is the high rate of recurrence caused by intrahepatic metastas is that adversely affects long-term outcome. Many studies have indicated that microRNAs play an important role in HCC, but there has been no research of clonal origins on recurrent HCC (RHCC) by analzing microRNAs. In the present study, we found that miR-483-5p was significantly upregulated in RHCC tissues of short-term recurrence (≤ 2 years) by miRNA microarray screening, and can significantly promote migration and invasion of HCC cells in vitro and increase intrahepatic metastasis in nude mice in vivo. Furthermore, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM), which significantly suppressed migration and invasion of HCC cells, was a direct target of miR-483-5p, and the re-introduction of ALCAM expression could antagonize the promoting effects of miR-483-5p on the capacity of HCC cells for migration and invasion. In addition, expression level of ALCAM was negatively correlated with microvascular invasion and tumor size recognized as prognostic factors. The cases which were negative for ALCAM expression had shorter time to recurrence than positive cases, and univariate and multivariate survival analyses showed that ALCAM was an independent risk factor of HCC recurrence. qRT-PCR and Western blotting showed that the expression of EMT related genes (MMP-2, MMP-9, E-caherin and vimentin) significantly changed as a result of interfering or overexpression of ALCAM, and ALCAM was significantly associated with EMT in HCC. These results suggest that the miR-483-5p/ALCAM axis is an important regulator in invasion and metastasis and biomarker for recurrence risk assessment of HCC.
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miR-483-5p通过靶向RhoGDI1和ALCAM促进肺腺癌的侵袭和转移
影响因子：
11.2
作者：
Song, Qiancheng;Xu, Yuanfei;Bai, Xiaochun
通讯作者：
Bai, Xiaochun
DOI：
10.1016/j.jamcollsurg.2013.07.402
发表时间：
2013-12-01
影响因子：
5.2
作者：
Wang, Bin;Xia, Chun-Yan;Wu, Meng-Chao
通讯作者：
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影响因子：
5.3
作者：
Li F;Ma N;Zhao R;Wu G;Zhang Y;Qiao Y;Han D;Xu Y;Xiang Y;Yan B;Jin J;Lv G;Wang L;Xu C;Gao X;Luo S
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Luo S
肝细胞癌静脉转移相关的差异组合调控网络分析。
影响因子：
4.4
作者：
Zeng L;Yu J;Huang T;Jia H;Dong Q;He F;Yuan W;Qin L;Li Y;Xie L
通讯作者：
Xie L
影响因子：
254.7
作者：
Torre, Lindsey A.;Bray, Freddie;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin