MicroRNA-30a-5p inhibits gallbladder cancer cell proliferation, migration and metastasis by targeting E2F7.
MicroRNA-30a-5p inhibits gallbladder cancer cell proliferation, migration and metastasis by targeting E2F7.
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MicroRNA-30a-5p通过靶向E2F7抑制胆囊癌细胞增殖、迁移和转移
DOI：
10.1038/s41419-018-0444-x
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发表时间：
2018-03-14
影响因子：
9
通讯作者：
Liu YB
中科院分区：
文献类型：
--
作者：
Ye YY;Mei JW;Xiang SS;Li HF;Ma Q;Song XL;Wang Z;Zhang YC;Liu YC;Jin YP;Hu YP;Jiang L;Liu FT;Zhang YJ;Hao YJ;Liu YB
胆囊癌（GBC）是最常见的胆管恶性肿瘤，具有高度侵袭性，预后差。microRNA-30 a-5 p（miR-30 a-5 p）是一种重要的肿瘤抑制因子，参与肿瘤发生和发展的多个方面。然而，miR-30 a-5 p在GBC发展中的作用仍有待确定，其在GBC中的作用机制也有待确定。使用从42名胆囊癌（GBC）受试者收集的样本，我们发现原发性病变与非肿瘤相邻组织（NAT）相比，miR-30 a-5 p表达降低。miR-30 a-5 p降低与较短的无病生存期（DFS）和总生存期（OS）相关。在2个代表性GBC细胞系（GBC-SD和NOZ）中抑制miR-30 a-5 p表达增加细胞增殖、迁移、侵袭以及β-连环蛋白核转位，反之亦然。在裸鼠中，用miR-30 a-5 p模拟物转染的NOZ细胞在皮下接种后生长较慢（相对于miR-NC），并且在脾接种后具有较低的肝转移率。双荧光素酶检测证实E2 F转录因子7（E2 F7）是miR-30 a-5 p的直接靶点，并能拮抗GBC细胞中miR-30 a-5 p下调所诱导的效应。MiR-30 a-5 p通过靶向E2 F7来减弱GBC细胞中的EMT和转移，这表明miR-30 a-5 p是一种肿瘤抑制因子，可作为GBC的新型潜在预后生物标志物或分子治疗靶点。
Gallbladder carcinoma (GBC), the most common malignant tumour of the bile duct, is highly aggressive and has a poor prognosis. MicroRNA-30a-5p (miR-30a-5p) is an important tumour suppressor that participates in many aspects of carcinogenesis and cancer development. However, the role of miR-30a-5p in GBC development remains to be determined, as do the mechanisms underlying its effects in GBC. Using samples collected from 42 subjects with gallbladder carcinoma (GBC), we showed decreased miR-30a-5p expression in the primary lesions vs. non-tumour adjacent tissues (NATs). Decreased miR-30a-5p was associated with shorter disease-free survival (DFS) and overall survival (OS). Inhibiting miR-30a-5p expression in 2 representative GBC cell lines (GBC-SD and NOZ) increased cell proliferation, migration, invasiveness, as well as β-catenin nuclear translocation, vice versa. In nude mice, NOZ cells transfected with miR-30a-5p mimics grew slower (vs. miR-NC) upon subcutaneous inoculation, and had lower rate of hepatic metastasis upon spleen inoculation. Dual luciferase assay confirmed that E2F transcription factor 7 (E2F7) was a direct target of miR-30a-5p and antagonized the effects induced by miR-30a-5p downregulation in GBC cells. MiR-30a-5p attenuates the EMT and metastasis in GBC cells by targeting E2F7, suggesting miR-30a-5p is a tumour suppressor that may serve as a novel potential prognostic biomarker or molecular therapeutic target for GBC.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
11.2
作者：
Kong, Kar Lok;Kwong, Dora L.;Guan, Xin-Yuan
通讯作者：
Guan, Xin-Yuan
影响因子：
--
作者：
Dong P;Ihira K;Xiong Y;Watari H;Hanley SJ;Yamada T;Hosaka M;Kudo M;Yue J;Sakuragi N
通讯作者：
Sakuragi N
影响因子：
--
作者：
Ning ZQ;Lu HL;Chen C;Wang L;Cai W;Li Y;Cao TH;Zhu J;Shu YQ;Shen H
通讯作者：
Shen H
miR-23b-3p通过靶向ATG12和HMGB2调节胃癌细胞的化疗耐药
影响因子：
9
作者：
An Y;Zhang Z;Shang Y;Jiang X;Dong J;Yu P;Nie Y;Zhao Q
通讯作者：
Zhao Q