长链非编码 RNA HCG11 通过 miR-26a-5p/ATG12 轴加速肝细胞癌的进展。
LncRNA HCG11 accelerates the progression of hepatocellular carcinoma via miR-26a-5p/ATG12 axis.
机构信息
Department of Radiology, the First Affiliated Hospital of Xi'An Jiaotong University, Xi'an, Shanxi, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Dec;23(24):10708-10720. doi: 10.26355/eurrev_201912_19771.
OBJECTIVE
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers globally. LncRNA HLA complex group 11 (HCG11) has been reported to play an oncogenic role in multiple cancers. Nevertheless, the role and regulatory mechanism of HCG11 in HCC are not fully addressed.
PATIENTS AND METHODS
The abundance of HCG11 and miR-26a-5p was measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) in HCC tissues and cells. Cell proliferation, apoptosis, metastasis, and autophagy were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, transwell migration, invasion assays, and Western blot assay, respectively. The binding sites between miR-26a-5p and HCG11 or autophagy-related 12 (ATG12) were predicted by starBase bioinformatic software, and the combination was confirmed by Dual-Luciferase reporter assay. The abundance of ATG12 was examined by Western blot assay. Murine xenograft model was established to validate the function of HCG11 in vivo.
RESULTS
The enrichment of HCG11 was enhanced in HCC tissues and cells and was negatively related to the prognosis of HCC patients. The abundance of miR-26a-5p was inversely correlated with the level of HCG11 in HCC tissues. HCG11 interference suppressed the proliferation, metastasis, and autophagy while promoted the apoptosis of HCC cells. MiR-26a-5p bound to lncRNA HCG11 and ATG12. The depletion of miR-26a-5p or the accumulation of ATG12 could alleviate the suppressive effects induced by HCG11 intervention on the proliferation, metastasis, autophagy, and the promoting impact on the apoptosis of HCC cells. HCG11 promoted the growth of murine xenograft tumor and autophagy through miR-26a-5p/ATG12 axis in vivo.
CONCLUSIONS
LncRNA HCG11 accelerated the proliferation, metastasis, and autophagy while impeded the apoptosis of HCC cells via HCG11/miR-26a-5p/ATG12 axis. HCG11 might be a potential therapeutic target for the treatment of HCC.
目的
肝细胞癌（HCC）是全球最常见的癌症之一。长链非编码 RNA HLA 复合体 11（HCG11）已被报道在多种癌症中发挥致癌作用。然而，HCG11 在 HCC 中的作用和调控机制尚未完全阐明。
方法
通过实时定量聚合酶链反应（qRT-PCR）测量 HCC 组织和细胞中 HCG11 和 miR-26a-5p 的丰度。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐（MTT）、流式细胞术、transwell 迁移、侵袭试验和 Western blot 试验分别检测细胞增殖、凋亡、转移和自噬。通过 starBase 生物信息学软件预测 miR-26a-5p 与 HCG11 或自噬相关 12（ATG12）的结合位点，并通过双荧光素酶报告基因试验证实其结合。Western blot 试验检测 ATG12 的丰度。建立小鼠异种移植模型以验证 HCG11 在体内的功能。
结果
HCG11 在 HCC 组织和细胞中的丰度增加，并与 HCC 患者的预后呈负相关。miR-26a-5p 在 HCC 组织中的丰度与 HCG11 的水平呈负相关。干扰 HCG11 可抑制 HCC 细胞的增殖、转移和自噬，促进其凋亡。miR-26a-5p 与 lncRNA HCG11 和 ATG12 结合。miR-26a-5p 耗竭或 ATG12 积累可减轻 HCG11 干预对 HCC 细胞增殖、转移、自噬的抑制作用，并促进其凋亡。HCG11 通过 miR-26a-5p/ATG12 轴在体内促进小鼠异种移植肿瘤的生长和自噬。
结论
lncRNA HCG11 通过 HCG11/miR-26a-5p/ATG12 轴加速 HCC 细胞的增殖、转移和自噬，同时抑制其凋亡。HCG11 可能是治疗 HCC 的潜在治疗靶点。
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