Key Laboratory of Laboratory Medicine, Ministry of Education of China, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
Department of Obstetrics-Gynecology, The First Hospital of Ningbo, Ningbo, Zhejiang, 315035, China.
BMC Cancer. 2018 Jan 9;18(1):61. doi: 10.1186/s12885-017-3753-z.
Around the world, cervical cancer is the fourth most common cancer among women. MicroRNAs (miRNAs) and agents that target mRNAs have been introduced as novel diagnostic markers and therapeutic approaches, respectively, in cancer. MiRNA-486-5p is a candidate regulator of phosphatase and tensin homolog (PTEN) in silico, and the downregulation of PTEN in cervical cancer is not consistent with its mutation, which suggests that PTEN may be subjected to post-transcription modification moderated by miRNAs. Here, we aimed to explore whether miR-486-5p is a regulator in the development of cervical cancer through the PI3K/Akt pathway by targeting PTEN.
The expression level of miR-486-5p in human cervical cancer serum and tissues were analyzed through quantitative RT-PCR. Human cervical cancer cell lines HeLa and SiHa were selected to explore the effects of miR-486-5p downregulated or overexpression on cell proliferation, migration, and invasion, respectively. Moreover, we observed the effect of miR-486-5p downregulated on tumorigenesis using HeLa cell in vivo. Besides, the relationship between miR-486-5p and PTEN were determined by dual luciferase reporter gene assay.
Compared to control subjects, miR-486-5p was significantly overexpressed in cervical cancer patients' serum and tissues. Suppression of miR-486-5p expression significantly inhibited HeLa cell proliferation, colony formation, migration, and invasion, as well as tumor growth in nude mice, while miR-486-5p overexpression stimulated SiHa cell proliferation, colony formation, migration, and invasion. We also confirmed that miR-486-5p directly targeted the 3'-untranslated region of the tumor-suppressor gene PTEN, inhibiting its expression, and that overexpression of miR-486-5p activated the PI3K/Akt pathway.
We conclude that miR-486-5p stimulates cell proliferation, migration, and invasion through inhibition of PTEN expression and activation of the oncogenic PI3K/Akt pathway in cervical cancer. Our findings implicate serum miR-486-5p as a novel molecular biomarker that may provide effective approaches to both diagnosis and treatment in cervical cancer.
在全球范围内，宫颈癌是女性中第四常见的癌症。microRNAs（miRNAs）和靶向 mRNAs 的药物分别作为新型诊断标志物和治疗方法被引入癌症领域。miRNA-486-5p 在计算机上是磷酸酶和张力蛋白同源物（PTEN）的候选调节因子，而宫颈癌中 PTEN 的下调与突变不一致，这表明 PTEN 可能受到 miRNA 介导的转录后修饰调节。在这里，我们旨在通过靶向 PTEN 探讨 miR-486-5p 是否通过 PI3K/Akt 途径成为宫颈癌发展的调节因子。
通过定量 RT-PCR 分析人宫颈癌血清和组织中 miR-486-5p 的表达水平。选择人宫颈癌细胞系 HeLa 和 SiHa，分别研究 miR-486-5p 下调或过表达对细胞增殖、迁移和侵袭的影响。此外，我们还观察了 miR-486-5p 下调对 HeLa 细胞体内致瘤性的影响。此外，通过双荧光素酶报告基因检测确定 miR-486-5p 与 PTEN 之间的关系。
与对照组相比，宫颈癌患者血清和组织中 miR-486-5p 表达明显上调。抑制 miR-486-5p 的表达显著抑制了 HeLa 细胞的增殖、集落形成、迁移和侵袭，以及裸鼠体内的肿瘤生长，而 miR-486-5p 的过表达刺激了 SiHa 细胞的增殖、集落形成、迁移和侵袭。我们还证实，miR-486-5p 可直接靶向肿瘤抑制基因 PTEN 的 3'-非翻译区，抑制其表达，而过表达 miR-486-5p 激活了致癌的 PI3K/Akt 通路。
我们得出结论，miR-486-5p 通过抑制 PTEN 表达和激活致癌的 PI3K/Akt 通路，刺激宫颈癌中的细胞增殖、迁移和侵袭。我们的研究结果表明，血清 miR-486-5p 是一种新的分子生物标志物，可能为宫颈癌的诊断和治疗提供有效的方法。
