Wang Li-Ping, Wang Jun-Ping, Wang Xin-Ping
Department of Medicine, Xi'an Honghui Hospital, Xi'an, Shaanxi 710068, P.R. China.
Department of Medicine, The Friendship Hospital of Shaanxi, Xi'an, Shaanxi 710000, P.R. China.
Oncol Lett. 2018 May;15(5):7963-7972. doi: 10.3892/ol.2018.8341. Epub 2018 Mar 23.
Non-coding RNAs are important in the progression of liver cancer. The present study aimed to investigate the effects of long non-coding RNA HOX transcript antisense RNA (HOTAIR) on the proliferation of liver cancer and the association between HOTAIR and microRNA (miR)-217. It was demonstrated that the expression of HOTAIR was upregulated in liver cancer tissues and 3 liver cancer cell lines (MHCC97H, HepG2 and Hep3B). Inhibition of HOTAIR with HOTAIR small interfering (si) RNA lentiviral vectors significantly suppressed the cell proliferation of HepG2 cells, and downregulated the protein expression levels of two proliferation markers, Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, inhibition of HOTAIR induced G0/G1 cycle arrest by increasing the expression of p27 and decreasing the expression of cyclin D1. It was then predicted and verified that miR-217 was the target of HOTAIR. Expression of miR-217 was downregulated in liver cancer tissues and the 3 liver cancer cell lines. Further results revealed that inhibition of HOTAIR markedly upregulated the expression of miR-217 in HepG2 cells, and miR-217 inhibitor-induced reduction of miR-217 was significantly suppressed by HOTAIR inhibition. Furthermore, the increased cell proliferation and growth, the upregulated expression of Ki67 and PCNA, and the reduced G0/G1 cycle arrest induced by miR-217 inhibitor were partly rescued by inhibition of HOTAIR. Finally, the experiment indicated that HOTAIR inhibition suppressed tumorigenesis, including the smaller tumor volume and the reduced levels of Ki67. Overall, HOTAIR contributes to the proliferation and growth of liver cancer via downregulation of miR-217.
非编码RNA在肝癌进展中具有重要作用。本研究旨在探讨长链非编码RNA HOX转录本反义RNA（HOTAIR）对肝癌细胞增殖的影响以及HOTAIR与微小RNA（miR）-217之间的关联。结果表明，HOTAIR在肝癌组织及3种肝癌细胞系（MHCC97H、HepG2和Hep3B）中表达上调。采用HOTAIR小干扰（si）RNA慢病毒载体抑制HOTAIR可显著抑制HepG2细胞的增殖，并下调两种增殖标志物Ki67和增殖细胞核抗原（PCNA）的蛋白表达水平。此外，抑制HOTAIR可通过增加p27的表达和降低细胞周期蛋白D1的表达诱导G0/G1期细胞周期阻滞。随后预测并验证miR-217是HOTAIR的靶点。miR-217在肝癌组织及这3种肝癌细胞系中表达下调。进一步结果显示，抑制HOTAIR可显著上调HepG2细胞中miR-217的表达，而HOTAIR抑制可显著抑制miR-217抑制剂诱导的miR-217表达降低。此外，抑制HOTAIR可部分挽救miR-217抑制剂诱导的细胞增殖和生长增加、Ki67和PCNA表达上调以及G0/G1期细胞周期阻滞减少的现象。最后，实验表明抑制HOTAIR可抑制肿瘤发生，包括减小肿瘤体积和降低Ki67水平。总体而言，HOTAIR通过下调miR-217促进肝癌的增殖和生长。
