MiR-130b plays an oncogenic role by repressing PTEN expression in esophageal squamous cell carcinoma cells

被引:93
作者
Yu, Tingting [1 ]
Cao, Risheng [1 ]
Li, Shuo [1 ]
Fu, Mingen [1 ]
Ren, Lihua [1 ]
Chen, Weixu [1 ]
Zhu, Hong [1 ]
Zhan, Qiang [2 ]
Shi, Ruihua [1 ,3 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp 1, Dept Gastroenterol, Nanjing 210029, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Wuxi Peoples Hosp, Dept Gastroenterol, Wuxi 214023, Peoples R China
[3] Southeast Univ, Zhongda Hosp, Dept Gastroenterol, Nanjing 210009, Jiangsu, Peoples R China
来源
BMC CANCER | 2015年 / 15卷
基金
中国国家自然科学基金;
关键词
Esophageal squamous cell carcinoma; miR-130b; Oncogenic; PTEN; TUMOR-SUPPRESSOR; PROGNOSTIC-SIGNIFICANCE; CANCER; MICRORNAS; PROMOTES; TARGETS; RESISTANCE; REGIONS; PROTEIN; GROWTH;
D O I
10.1186/s12885-015-1031-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Esophageal carcinoma is one of the most common malignancies with high cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate a wide variety of cellular processes, and also play an important role in the development and progression of cancers. In a previous microarray study, we demonstrated that miR-130b was upregulated in esophageal squamous cell carcinoma (ESCC) tissues. However, the biologic functions and the molecular mechanism of miR-130b in ESCC remain to be elucidated. Methods: qRT-PCR assays were used to quantify miR-130b expression levels in ESCC samples. Novel targets of miR-130b were identified via a bioinformatics search and confirmed using a dual-luciferase reporter system. Western blotting and qRT-PCR assays were used to quantify the expression of the target gene PTEN (phosphatase and tensin homolog) and the downstream effector, Akt. ESCC cells over-or underexpressing miR-130b were analyzed for in vitro biologic functions. Results: High levels of miR-130b were identified in 20 ESCC samples following comparison with adjacent non-neoplastic tissues. We confirmed that miR-130b interacted with the 3'-untranslated region of PTEN, and that an increase in the expression level of miR-130b negatively affected the protein level of PTEN. However, the dysregulation of miR-130b had no obvious impact on PTEN mRNA. As Akt is a downstream effector of PTEN, we explored if miR-130b affected Akt expression, and found that miR-130b indirectly regulated the level of phosphorylated Akt, while total Akt protein remained unchanged. Overexpression of miR-130b increased the proliferation of ESCC cells and enhanced their ability to migrate and invade. In contrast, the proliferation, migration, and invasion of ESCC cells were weakened when miR-130b expression was suppressed, which was reversed by PTEN-targeted siRNA. Conclusion: The results indicate that miR-130b plays an oncogenic role in ESCC cells by repressing PTEN expression and Akt phosphorylation, which would be helpful in developing miRNA-based treatments for ESCC.
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页数:9
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