PTENP1 作为 ceRNA 通过海绵吸附 miR-19b 来调节 PTEN，并探索了 PTENP1 在乳腺癌中的生物学作用。
PTENP1 acts as a ceRNA to regulate PTEN by sponging miR-19b and explores the biological role of PTENP1 in breast cancer.
机构信息
Department of Clinical Laboratory, Shantou University Medical College, Shantou, Guangdong, China.
Department of Clinical Laboratory, The Second People's Hospital of Baoan District of Shenzhen, Shenzhen, Guangdong, China.
出版信息
Cancer Gene Ther. 2017 Jul;24(7):309-315. doi: 10.1038/cgt.2017.29. Epub 2017 Jul 21.
This study aimed to investigate role of long noncoding RNA PTENP1 regulating PTEN expression via miR-19b to affect breast cancer (BC) progression. We measured expressions of PTENP1, miR-19b and PTEN in 65 matched BC cancerous and noncancerous tissues by quantitative real-time fluorescence PCR (qRT-PCR) and investigated the biological effects of PTENP1 in BC MDA-MB-231 cells by several in vitro experiments including CCK8, wound healing, transwell and Annexin V-FITC/PI analysis. Besides, the competing endogenous RNA (ceRNA) activity of PTENP1 on miR-19b was detected by luciferase reporter assay, and the expressions of related genes and proteins were determined by western blot assay and qRT-PCR. Increased PTENP1 and PTEN and decreased miR-19b were observed in BC tissues and cell lines. Further, PTENP1 and PTEN are direct targets of miR-19b, and overexpressed PTENP1 in MDA-MB-231 cells could supress cell proliferation, migration and invasion and promote cell apoptosis. Moreover, PTENP1 could upregulate PTEN via its ceRNA interaction on miR-19b, as well as induced the upregulation of p53 and downregulation of p-AKT. Enhanced PTENP1 could inhibit BC cell growth, metastasis and tumourigenicity by inhibiting miR-19b and facilitating PTEN in BC, thereby may represent a novel target for diagnosis and treatment of BC.
本研究旨在探讨长链非编码 RNA PTENP1 通过 miR-19b 调控 PTEN 表达从而影响乳腺癌（BC）进展的作用。我们通过定量实时荧光 PCR（qRT-PCR）测量了 65 对匹配的 BC 癌组织和非癌组织中 PTENP1、miR-19b 和 PTEN 的表达，并通过 CCK8、划痕愈合、Transwell 和 Annexin V-FITC/PI 分析等多种体外实验研究了 PTENP1 在 BC MDA-MB-231 细胞中的生物学效应。此外，通过荧光素酶报告基因实验检测了 PTENP1 对 miR-19b 的竞争性内源性 RNA（ceRNA）活性，并通过 Western blot 实验和 qRT-PCR 测定了相关基因和蛋白的表达。在 BC 组织和细胞系中观察到 PTENP1 和 PTEN 升高，miR-19b 降低。进一步研究表明，PTENP1 和 PTEN 是 miR-19b 的直接靶基因，在 MDA-MB-231 细胞中过表达 PTENP1 可抑制细胞增殖、迁移和侵袭，促进细胞凋亡。此外，PTENP1 可通过其与 miR-19b 的 ceRNA 相互作用上调 PTEN，并诱导 p53 上调和 p-AKT 下调。增强的 PTENP1 通过抑制 miR-19b 促进 PTEN 在 BC 中的表达，从而抑制 BC 细胞生长、转移和致瘤性，因此可能成为 BC 诊断和治疗的新靶点。
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