Department of Hepatobiliary Surgery, Weifang People's Hospital, Weifang, China.
Department of Anaesthesiology, Weifang People's Hospital, Weifang, China.
J Cell Biochem. 2019 Oct;120(10):17757-17766. doi: 10.1002/jcb.29041. Epub 2019 May 29.
BACKGROUND/AIMS: High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines.
The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied.
As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p.
HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.
背景/目的:高表达于肝癌(HEIH)的长链非编码 RNA(lncRNA)在肝癌(HCC)中高度表达。HEIH 的异常表达被认为参与调节 HCC 细胞的生长和转移。本研究试图阐明 HEIH 对 HCC 细胞系的影响。
检测了 20 例 HCC 患者肿瘤组织和癌旁组织中 HEIH 的表达变化。通过体外沉默 HEIH 评估 HEIH 对 Huh7 和 Hep3B 细胞活力、凋亡、迁移和侵袭的影响。此外,还研究了 HEIH 的下游效应物和信号通路。
与癌旁组织相比,肿瘤组织中 HEIH 的表达明显升高。沉默 HEIH 显著降低 Huh7 和 Hep3B 细胞的活力、迁移和侵袭,但诱导凋亡。这伴随着 CyclinD1、Bcl-2、MMP-2、MMP-8、波形蛋白的下调,p53、Bax 的上调,以及 cleaved caspase-3 的激活。MicroRNA(miR)-199a-3p 被鉴定为 HEIH 的下游效应物,因为其表达被 HEIH 沉默上调,并且当抑制 miR-199a-3p 的表达时,HEIH 对 Huh7 和 Hep3B 细胞的功能作用都减弱。此外,HEIH 沉默通过上调 miR-199a-3p 抑制 mTOR 信号通路的激活。
沉默 HEIH 可能是抑制 HCC 细胞生长和转移的有前途的靶点。沉默 HEIH 通过上调 miR-199a-3p 发挥其抗肿瘤特性,从而阻断 mTOR 信号通路。