MicroRNA-30a-5p inhibits gallbladder cancer cell proliferation, migration and metastasis by targeting E2F7

作者：Ye, Yuan-Yuan; Mei, Jia-Wei; Xiang, Shan-Shan; Li, Huai-Feng; Ma, Qiang; Song, Xiao-Ling; Wang, Zheng; Zhang, Yi-Chi; Liu, Yong-Chen; Jin, Yun-Peng; Hu, Yun-Ping; Jiang, Lin; Liu, Fa-Tao; Zhang, Yi-Jian; Hao, Ya-Juan^*; Liu, Ying-Bin^*

来源：Cell Death & Disease, 2018, 9(3): 410.

DOI：10.1038/s41419-018-0444-x

• EPITHELIAL-MESENCHYMAL TRANSITION
• TUMOR-SUPPRESSOR
• DOWN-REGULATION
• BREAST-CANCER
• LUNG-CANCER
• CARCINOMA
• PATHWAY
• REPRESSION
• GROWTH
• CONTRIBUTES

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 beta-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-30a5p 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.

• 出版日期2018-3-14
• 单位上海交通大学