Objective. To investigate the expression of long noncoding RNA lysyl oxidase-like 1-antisense 1 (LOXL1-AS1) in hepatocellular carcinoma tissues and its effect on cell proliferation, migration, and invasion. Methods. Quantitative real-time PCR was used to analyze the expression of LOXL1-AS1 RNA in tumor tissues, adjacent normal tissues, and cell lines. MTT assay, colony formation assay, flow cytometry analysis, transwell assays, and lentivirus-mediated RNA interference (RNAi) technology were used to evaluate cell proliferation and migration. Results. In the present study, we observed that the expression level of LOXL1-AS1 in hepatocellular carcinoma tissue was significantly higher than that in adjacent nontumor tissues, and its expression in three hepatic carcinoma cell lines was obviously higher than that in a normal cell line. In addition, in the Hep-G2 cell line, LOXL1-AS1 downregulation significantly inhibited cell proliferation in the light of the MTT and colony formation assays in vitro, which was consistent with animal experiment in vivo. What is more, cell migration was also inhibited in vitro in Matrigel Transwell Assay by LOXL1-AS1 knockdown, which might be partly attributed to the reduction of MMP-2 and MMP-9 protein expressions. Finally, cell cycle analysis revealed that knockdown of LOXL1-AS1 induced significantly a G0/G1 phase cell cycle arrest, which might be partly attributed to the downregulation of Cdc2, Cdc25A, and cyclin B1 protein expression. Conclusion. In conclusion, we demonstrated that reduced LOXL1-AS1 expression could inhibit hepatocellular carcinoma cell proliferation, migration, and invasion. The application of RNAi targeting LOXL1-AS1 might be a potential treatment strategy in advanced cases.

中文翻译：

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长链非编码 RNA LOXL1-AS1 促进肝细胞癌的增殖、迁移和侵袭

客观。研究长链非编码RNA赖氨酰氧化酶样1-反义1（LOXL1-AS1）在肝癌组织中的表达及其对细胞增殖、迁移和侵袭的影响。方法。定量实时PCR用于分析LOXL1-AS1 RNA在肿瘤组织、邻近正常组织和细胞系中的表达。MTT 测定、集落形成测定、流式细胞术分析、transwell 测定和慢病毒介导的 RNA 干扰 (RNAi) 技术用于评估细胞增殖和迁移。结果. 在本研究中，我们观察到LOXL1-AS1在肝细胞癌组织中的表达水平显着高于邻近的非肿瘤组织，并且在3个肝癌细胞系中的表达明显高于在正常细胞系中的表达。此外，根据MTT和体外集落形成试验，在Hep-G2细胞系中，LOXL1-AS1下调显着抑制细胞增殖，这与体内动物实验一致。此外，通过 LOXL1-AS1 敲低，在 Matrigel Transwell Assay 中，细胞迁移在体外也受到抑制，这可能部分归因于 MMP-2 和 MMP-9 蛋白表达的降低。最后，细胞周期分析显示，敲低 LOXL1-AS1 显着诱导 G0/G1 期细胞周期停滞，结论。总之，我们证明了降低的 LOXL1-AS1 表达可以抑制肝细胞癌细胞的增殖、迁移和侵袭。靶向 LOXL1-AS1 的 RNAi 的应用可能是晚期病例的潜在治疗策略。