Cao Jing, Yang Zhenming, An Ran, Zhang Jiarui, Zhao Rui, Li Wenjing, Xu Licheng, Sun Yanan, Liu Ming, Tian Linli
Department of Otorhinolaryngology, Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China.
Cancer Sci. 2020 Sep;111(9):3245-3257. doi: 10.1111/cas.14559. Epub 2020 Jul 30.
Because advanced laryngeal squamous cell carcinoma (LSCC) is diagnosed as a malignant tumor with a poor prognosis, the associated mechanisms still need to be further investigated. As key players in the development and progression of LSCC, lncRNAs have attracted increasing attention from many researchers. In this study, a novel lncRNA termed IGKJ2-MALLP2 was identified and investigated for its effects on the development of LSCC. IGKJ2-MALLP2 expression was confirmed by RT-qPCR in 78 pairs of tissues and human laryngeal carcinoma cell lines. The results of this study showed that the expression of IGKJ2-MALLP2 was reduced in LSCC tissues and displayed close relationships with tumor stage, lymph node metastasis, and clinical stage. Using a dual-luciferase reporter assay, the ability of miR-1911-3p to bind both IGKJ2-MALLP2 and p21 mRNA was demonstrated. IGKJ2-MALLP2 could upregulate p21 expression by competitively binding miR-1911-3p. Moreover, IGKJ2-MALLP2 effectively hindered the invasion, migration, and proliferation of AMC-HN-8 and TU212 tumor cells. Furthermore, its high expression could hinder the secretion of VEGF-A and suppress angiogenesis. As revealed by the results of in vitro experiments, IGKJ2-MALLP2 overexpression could restrict tumor growth and blood vessel formation in a xenograft model of LSCC. As indicated from the mentioned findings, IGKJ2-MALLP2, which mediates p21 expression by targeting miR-1911-3p, was capable of regulating LSCC progression and could act as an underlying therapeutic candidate to treat LSCC.
由于晚期喉鳞状细胞癌(LSCC)被诊断为预后较差的恶性肿瘤,其相关机制仍需进一步研究。作为LSCC发生和发展的关键因素,长链非编码RNA(lncRNAs)已引起众多研究人员越来越多的关注。在本研究中,一种名为IGKJ2 - MALLP2的新型lncRNA被鉴定并研究了其对LSCC发展的影响。通过RT - qPCR在78对组织和人喉癌细胞系中证实了IGKJ2 - MALLP2的表达。本研究结果表明,IGKJ2 - MALLP2在LSCC组织中的表达降低,且与肿瘤分期、淋巴结转移和临床分期密切相关。使用双荧光素酶报告基因测定法,证明了miR - 1911 - 3p与IGKJ2 - MALLP2和p21 mRNA均具有结合能力。IGKJ2 - MALLP2可通过竞争性结合miR - 1911 - 3p上调p21的表达。此外,IGKJ2 - MALLP2有效地抑制了AMC - HN - 8和TU212肿瘤细胞的侵袭、迁移和增殖。此外,其高表达可抑制血管内皮生长因子 - A(VEGF - A)的分泌并抑制血管生成。体外实验结果显示,在LSCC异种移植模型中,IGKJ2 - MALLP2过表达可限制肿瘤生长和血管形成。从上述研究结果表明,通过靶向miR - 1911 - 3p介导p21表达的IGKJ2 - MALLP2能够调节LSCC的进展,并可作为治疗LSCC的潜在治疗靶点。