Department of Hepatobiliary Surgery, The First Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Fuxing 28 Road, 1000853, Beijing, China.
Department of Oncology, The First Medical Centre, Chinese PLA (People's Liberation Army) General Hospital, Fuxing 28 Road, 1000853, Beijing, China.
Biomed Pharmacother. 2020 May;125:109916. doi: 10.1016/j.biopha.2020.109916. Epub 2020 Feb 12.
To date, a large set of long non-coding RNAs (lncRNAs) have been identified in tumorigenesis and progression. The present study focused on functions and mechanisms of HEIH in cholangiocarcinoma (CHOL). We started this study by testing the expression of HEIH in CHOL tissues by qRT-PCR technology. Next, loss-of-function experiments demonstrated the oncogenic nature of HEIH in CHOL. We also used bioinformatics tools to select miRNAs and mRNAs for support of the ceRNA network. Mechanistic experiments including RIP assay, luciferase reporter assay were carried out for further confirmation of binding situation among ceRNA molecules. At last, rescue experiments proved the ceRNA axis in CHOL. According to the results, HEIH expression was up-regulated in CHOL tissues and cells. Functionally, knockdown of HEIH attenuated cell proliferation, migration and invasion. Mechanistically, bioinformatics analysis, RIP assay and luciferase assay verified the ceRNA network among HEIH, miR-98-5p and HECTD4. Rescue experiments further demonstrated the oncogenic role of HEIH and HECTD4. The final in vivo experiments suggested that knockdown of HEIH restrained tumor growth both in weight and volume. In conclusion, HEIH promoted CHOL tumorigenesis and progression by miR-98-5p/HECTD4 axis, which opens up a new insight for CHOL therapeutics.
迄今为止，大量的长链非编码 RNA（lncRNAs）已被鉴定与肿瘤发生和进展有关。本研究主要关注 HEIH 在胆管癌（CHOL）中的功能和作用机制。我们首先通过 qRT-PCR 技术检测了 HEIH 在 CHOL 组织中的表达。接下来，通过功能丧失实验证明了 HEIH 在 CHOL 中的致癌性质。我们还使用生物信息学工具选择了 miRNA 和 mRNAs 来支持 ceRNA 网络。通过 RIP 实验和荧光素酶报告基因实验进行了机制实验，以进一步证实 ceRNA 分子之间的结合情况。最后，通过挽救实验证明了 ceRNA 轴在 CHOL 中的作用。结果表明，HEIH 在 CHOL 组织和细胞中呈高表达。功能上，HEIH 的敲低可减弱细胞的增殖、迁移和侵袭。通过生物信息学分析、RIP 实验和荧光素酶报告基因实验证实了 HEIH、miR-98-5p 和 HECTD4 之间的 ceRNA 网络。挽救实验进一步证实了 HEIH 和 HECTD4 的致癌作用。最后的体内实验表明，HEIH 的敲低可抑制肿瘤的生长（无论是在重量还是体积上）。总之，HEIH 通过 miR-98-5p/HECTD4 轴促进了 CHOL 的肿瘤发生和进展，为 CHOL 的治疗提供了新的思路。
