Ma H L, Wen X P, Zhang X Z, Wang X L, Zhao D L, Che S M, Dang C X
Xi'an Jiaotong University Department of Radiation Oncology, the First Affiliated Hospital of Medical Colledge, Shaanxi Xi'an China.
Xi'an Jiaotong University Department of Thoracic Surgery, the First Affiliated Hospital of Medical Colledge Shaanxi Xi'an China.
Cell Mol Biol (Noisy-le-grand). 2015 Aug 28;61(4):56-62.
Previous studies suggest that aberrant microRNA expression is common in plenty of cancers. The expression of miR-106a* was decreased in follicular lymphoma, but the expression and functions of miR-106a* in esophageal carcinoma (EC) remain unclear. In this study, we explored the expression and anti-oncogenic roles of miR-106a* in human EC. The expression of miR-106a* is significantly decreased in EC tissues and EC cell lines. Overexpression of miR-106a* suppressed EC cell proliferation, clonogenicity, G1/S transition, and induced apoptosis in vitro, but inhibition of miR-106a* facilitated cell proliferation, clonogenicity, G1/S transition. Luciferase reporter assay results showed that CDK2-associated Cullin 1 (CACUL1) was a direct target of miR-106a* in EC cells. Moreover, silencing CACUL1 resulted in the same biologic effects of miR-106a* overexpression in EC cells, which included suppressed EC cell proliferation, clonogenicity, and blocked G1/S transition through CDK2 pathway by inhibiting cell cycle regulators (Cyclin A, Cyclin E). Our data indicate that miR-106a* might play an anti-oncogenic role in EC by regulating CACUL1 expression, which suggest miR-106a* as a new potential diagnostic and therapeutic target for EC.
先前的研究表明，异常的微小RNA表达在许多癌症中很常见。miR-106a在滤泡性淋巴瘤中的表达降低，但miR-106a在食管癌（EC）中的表达及功能仍不清楚。在本研究中，我们探讨了miR-106a在人食管癌中的表达及抑癌作用。miR-106a在食管癌组织和食管癌细胞系中的表达显著降低。miR-106a的过表达在体外抑制了食管癌细胞的增殖、克隆形成能力、G1/S期转换并诱导了细胞凋亡，但抑制miR-106a则促进了细胞增殖、克隆形成能力及G1/S期转换。荧光素酶报告基因检测结果显示，CDK2相关的Cullin 1（CACUL1）是食管癌细胞中miR-106a的直接靶点。此外，沉默CACUL1在食管癌细胞中产生了与miR-106a过表达相同的生物学效应，包括抑制食管癌细胞增殖、克隆形成能力，并通过抑制细胞周期调节因子（细胞周期蛋白A、细胞周期蛋白E）阻断CDK2途径的G1/S期转换。我们的数据表明，miR-106a可能通过调节CACUL1的表达在食管癌中发挥抑癌作用，这提示miR-106a作为食管癌一种新的潜在诊断和治疗靶点。
