Long Noncoding RNA IGF2AS is Acting as an Epigenetic Tumor Suppressor in Human Prostate Cancer
Long Noncoding RNA IGF2AS is Acting as an Epigenetic Tumor Suppressor in Human Prostate Cancer
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长非编码 RNA IGF2AS 在人类前列腺癌中充当表观遗传肿瘤抑制因子。
DOI：
10.1016/j.urology.2018.11.002
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发表时间：
2019-02-01
期刊：
影响因子：
2.1
通讯作者：
Yang, Xiaorong
中科院分区：
文献类型：
--
作者：
Chen, Qiang;Sun, Ting;Yang, Xiaorong
目的探讨长非编码RNA(LncRNA)胰岛素生长因子2反义(IGF2AS)基因在前列腺癌(PCa)中的表达及其作用机制。方法采用定量逆转录聚合酶链式反应(QRT-PCR)检测前列腺癌(PCa)永生化细胞系和原位肿瘤中IGF2AS的表达。在VCaP和PC3细胞中过表达IGF2AS，观察IGF2AS对PCa细胞体外增殖和侵袭以及体内异种移植的影响。在PCa细胞中也检测了IGF2AS过表达对IGF2的影响。然后，IGF2在IGF2AS过表达的PCa细胞中上调，以评估IGF2在IGF2AS介导的PCa细胞发育中的作用。在VCaP和PC3细胞中，慢病毒诱导的IGF2AS过表达在体外抑制了癌细胞的增殖和侵袭，在体内抑制了异种移植瘤的发展。IGF2AS过表达下调了IGF2的表达。相反，IGF2AS上调IGF2AS对PCa增殖和侵袭的抑制作用。结论lncRNA IGF2AS可能通过对IGF2的反向调控在人PCa中发挥表观遗传肿瘤抑制作用。IGF2AS/IGF2轴可能是未来前列腺癌治疗的治疗靶点。(C)2018年Elsevier Inc.
OBJECTIVE To assess the expression profile and functional mechanism of long noncoding RNA (lncRNA) insulin growth factor 2 antisense (IGF2AS) in human prostate cancer (PCa).METHODS Quantitative reverse transcriptase-polymerase chain reaction was applied to assess IGF2AS expression in immortal PCa cell lines and in situ human PCa tumors. IGF2AS was overexpressed in VCaP and PC3 cells to assess its effect on PCa cell proliferation and invasion in vitro, and xenograft in vivo. The effect of IGF2AS overexpression on IGF2 was also assessed in PCa cells. Then, IGF2 was upregulated in IGF2AS-overexpressed PCa cells to assess the functional involvement of IGF2 in IGF2AS-mediated PCa cell development.RESULTS IGF2AS was downregulated in both PCa cell lines and human PCa tumors. In VCaP and PC3 cells, lentivirus-induced IGF2AS overexpression suppressed cancer cell proliferation and invasion in vitro, and xenograft development in vivo. IGF2 was downregulated by IGF2AS overexpression. Conversely, IGF2 upregulation revered the suppressing function of IGF2AS on PCa proliferation and invasion.CONCLUSION LncRNA IGF2AS is acting as an epigenetic tumor suppressor in human PCa, likely through inverse regulation on IGF2. IGF2AS/IGF2 axis may be a future therapeutic target for PCa treatment.(C) 2018 Elsevier Inc.