Liu Chong, Shang Zhonghua, Ma Yu, Ma Jianfang, Song Jian
Department of General Surgery, Second Hospital of Shanxi Medical University Taiyuan, Shanxi, China.
Department of General Surgery, Tai Yuan City Central Hospital Taiyuan, Shanxi, China.
Int J Clin Exp Pathol. 2019 Jan 1;12(1):50-63. eCollection 2019.
Long non-coding RNA (lncRNA) Hox transcript antisense intergenic RNA (HOTAIR) has been reported to play an important role in hepatocellular carcinoma (HCC) progression. Although there is evidence on HOTAIR being associated with HCC progression, the underlying mechanism remains to be further clarified.
HOTAIR, miR-214-3p and FLOT1 expression were measured by quantitative real-time PCR or western blot. Cell proliferation, migration, and invasion were displayed by transwell assay, MTT, and colony formation assay. The relationship between HOTAIR, miR-214-3p, and FLOT1 was investigated by luciferase reporter assay. Tumor suppressive effect of HOTAIR was displayed by HepG2 xenografting to nude mice.
HOTAIR and FLOT1 expression were significantly up-regulated, whereas miR-214-3p was obviously down-regulated. Also, down-regulation of HOTAIR and FLOT1 as well as up-regulation of miR-214-3p inhibited cell proliferation, invasion, and migration. Intriguingly, the effects of miR-214-3p overexpression on HCC cells were rescued by high expression of HOTAIR. Otherwise, HOTAIR regulated FLOT1 expression through targeting miR-214-3p in HCC cells. Simultaneously, low HOTAIR expression inhibited FLOT1 expression by up-regulating miR-214-3p, which suppressed tumor growth in vivo.
HOTAIR expression indirectly regulated FLOT1 expression through endogenous competition with miR-214-3p. HOTAIR/miR-214-3p/FLOT1 axis affected the cell proliferation, migration, and invasion of HCC.
据报道，长链非编码RNA（lncRNA）Hox转录本反义基因间RNA（HOTAIR）在肝细胞癌（HCC）进展中起重要作用。尽管有证据表明HOTAIR与HCC进展相关，但其潜在机制仍有待进一步阐明。
通过定量实时PCR或蛋白质免疫印迹法检测HOTAIR、miR-214-3p和FLOT1的表达。通过Transwell实验、MTT法和集落形成实验检测细胞增殖、迁移和侵袭能力。通过荧光素酶报告基因实验研究HOTAIR、miR-214-3p和FLOT1之间的关系。通过将HepG2细胞异种移植到裸鼠体内来显示HOTAIR的肿瘤抑制作用。
HOTAIR和FLOT1表达显著上调，而miR-214-3p明显下调。此外，HOTAIR和FLOT1的下调以及miR-214-3p的上调抑制了细胞增殖、侵袭和迁移。有趣的是，HOTAIR的高表达挽救了miR-214-3p过表达对HCC细胞的影响。此外，HOTAIR通过靶向miR-214-3p调节HCC细胞中FLOT1的表达。同时，低HOTAIR表达通过上调miR-214-3p抑制FLOT1表达，从而在体内抑制肿瘤生长。
HOTAIR表达通过与miR-214-3p的内源性竞争间接调节FLOT1表达。HOTAIR/miR-214-3p/FLOT1轴影响HCC细胞的增殖、迁移和侵袭。
