Chen Qin-Nan, Chen Xin, Chen Zhen-Yao, Nie Feng-Qi, Wei Chen-Chen, Ma Hong-Wei, Wan Li, Yan Shuai, Ren Sheng-Nan, Wang Zhao-Xia
Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210011, People's Republic of China.
Department of Pathology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
Mol Cancer. 2017 Jan 21;16(1):17. doi: 10.1186/s12943-017-0581-3.
Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown.
Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24.
LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD.
Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.
众多研究表明，长链非编码RNA（lncRNAs）在多种癌症进程中，如细胞增殖、凋亡、迁移和侵袭，表现为一类新型转录本。LINC00152位于2号染色体p11.2上，转录长度为828个核苷酸。LINC00152在肺腺癌（LAD）中的生物学作用尚不清楚。
采用定量逆转录PCR（qRT-PCR）检测60例人LAD组织及配对正常组织中LINC00152的表达。体外和体内研究显示了LINC00152在肿瘤进展中的生物学功能。运用RNA转录组测序技术鉴定下游抑制因子白细胞介素24（IL24），并通过qRT-PCR、蛋白质免疫印迹法和拯救实验进一步检测。进行RNA免疫沉淀（RIP）、RNA下拉和染色质免疫沉淀（ChIP）分析，以揭示LINC00152、EZH2和IL24之间的相互作用。
LINC00152在60例人LAD组织及配对正常组织中表达上调。LINC00152高表达与晚期TNM分期、更大肿瘤大小、淋巴结转移以及较短生存时间相关。沉默LINC00152可抑制细胞生长并诱导细胞凋亡。敲低LINC00152改变了许多下游基因的表达，包括IL24。LINC00152可与EZH2相互作用并抑制IL24转录。此外，IL24的异位表达抑制细胞增殖，并部分逆转LINC00152过表达诱导的LAD细胞生长促进作用。
我们的研究揭示了LINC00152在LAD肿瘤发生中的致癌作用，表明它可作为LAD治疗的一个治疗靶点。
