Department of Thyroid and Breast Surgery, Jining No. 1 People's Hospital, Affiliated Jining No. 1 People's Hospital of Jining Medical University, Jining Medical University, No. 6 Jiankang Road, Jining, 272000, Shandong, China.
Hum Cell. 2019 Oct;32(4):522-528. doi: 10.1007/s13577-019-00273-1. Epub 2019 Aug 27.
Hepatocellular carcinoma up-regulated EZH2-associated long non-coding RNA (HEIH) is a newly discovered lncRNA and has been suggested to be dysregulated in human cancers. However, the role of HEIH in triple-negative breast cancer (TNBC) was still unknown. Thus, the aim of our study was to investigate the clinical significance and biological function of HEIH in TNBC. In our study, we found that HEIH was overexpressed in TNBC tissues and cell lines compared with adjacent normal mammary tissues and normal mammary epithelial cell line, respectively. In addition, we conducted bioinformatic analysis, and found that HEIH harbors a potential miR-4458-binding site. Furthermore, we observed that HEIH and miR-4458 had a high correlation score in TNBC tissues, and HEIH directly binds to miR-4458, and negatively regulates miR-4458 expression in TNBC cells. The in vitro cell proliferation and apoptosis assays suggested down-regulation of HEIH inhibited TNBC cell proliferation and promoted apoptosis through regulating miR-4458/SOCS1 axis. Finally, we found that TNBC patients with tumor size ≥ 5 cm or advanced clinical stage had higher levels of HEIH expression than patients with tumor size < 5 cm or early clinical stage. In conclusion, HEIH functions as an oncogenic lncRNA that is overexpressed in TNBC and associated with clinical progression, and regulates TNBC cell proliferation and apoptosis through miR-4458/SOCS1 axis.
肝细胞癌上调 EZH2 相关长非编码 RNA (HEIH) 是一种新发现的 lncRNA，已被证明在人类癌症中失调。然而，HEIH 在三阴性乳腺癌 (TNBC) 中的作用尚不清楚。因此，本研究旨在探讨 HEIH 在 TNBC 中的临床意义和生物学功能。在本研究中，我们发现与相邻正常乳腺组织和正常乳腺上皮细胞系相比，HEIH 在 TNBC 组织和细胞系中表达上调。此外，我们进行了生物信息学分析，发现 HEIH 含有一个潜在的 miR-4458 结合位点。此外，我们观察到 HEIH 和 miR-4458 在 TNBC 组织中有很高的相关评分，HEIH 直接与 miR-4458 结合，并负调控 TNBC 细胞中 miR-4458 的表达。体外细胞增殖和凋亡实验表明，下调 HEIH 通过调控 miR-4458/SOCS1 轴抑制 TNBC 细胞增殖并促进凋亡。最后，我们发现肿瘤大小≥5cm 或临床分期较晚的 TNBC 患者的 HEIH 表达水平高于肿瘤大小<5cm 或临床分期较早的患者。总之，HEIH 作为一种癌基因 lncRNA 在 TNBC 中过度表达，与临床进展相关，并通过 miR-4458/SOCS1 轴调节 TNBC 细胞增殖和凋亡。
