LINC00239 Interacts with C-Myc Promoter-Binding Protein-1 (MBP-1) to Promote Expression of C-Myc in Esophageal Squamous Cell Carcinoma
LINC00239 Interacts with C-Myc Promoter-Binding Protein-1 (MBP-1) to Promote Expression of C-Myc in Esophageal Squamous Cell Carcinoma
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DOI：
10.1158/1541-7786.mcr-20-1025
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发表时间：
2021-09-01
影响因子：
5.2
通讯作者：
Guo, Wei
中科院分区：
文献类型：
--
作者：
Liang, Xiaoliang;Lu, Juntao;Guo, Wei
越来越多的证据表明，长链非编码RNA（lncRNA）在肿瘤（包括食管鳞状细胞癌（ESCC））的发展中起着至关重要的作用。LINC 00239被报道为多种癌症中的癌基因，而其在ESCC中的具体作用尚不清楚。本研究检测了LINC 00239在ESCC组织和细胞中的表达及其功能作用，并探讨了LINC 00239在ESCC组织和细胞中的高表达及其分子机制，LINC 00239与ESCC患者预后不良有关。LINC 00239过表达的ESCC细胞增殖、转移、侵袭能力以及上皮-间质转化（EMT）过程均增强。LINC 00239在TGF-β 1处理的ESCC细胞中上调。此外，发现LINC 00239直接结合到转录因子c-Myc启动子结合蛋白-1（MBP-1）。MBP-1可抑制食管鳞癌中c-Myc基因的转录。此外，LINC 00239可通过影响MBP- 1与c-Myc启动子的结合能力来激活c-Myc的转录。提示LINC 00239可能作为癌基因通过竞争性结合MBP-1促进c-Myc基因在食管鳞癌中的转录，并可能成为食管鳞癌抗肿瘤治疗的潜在靶点。
Increasing evidence demonstrates that long non-coding RNAs (lncRNA) play a vital role in the progression of tumors, containing esophageal squamous cell carcinoma (ESCC). LINC00239 was reported as an oncogene in diverse kinds of cancers, whereas its specific role is still unclear in ESCC. In this study, we detected the expression and functional role of LINC00239 in ESCC specimens and cells, and investigated the molecular mechanisms of it. LINC00239 was highly expressed in ESCC tissues and cells, and was related to poor prognosis of patients with ESCC. The proliferation, metastasis, and invasion ability as well as epithelial-mesenchymal transition (EMT) process were all enhanced in LINC00239-overexpressed ESCC cells. LINC00239 was upregulated in TGF-b1-treated ESCC cells. Furthermore, LINC00239 was found to bind directly to the transcription factor c-Myc promoter-binding protein-1 (MBP-1). MBP-1 was detected to inhibit the transcription of c-Myc in ESCC. Moreover, LINC00239 could activate c-Myc transcription through influencing MBP- 1-binding ability to c-Myc promoter. These data suggest that LINC00239 may act as an oncogene to promote the transcription of c-Myc by competitively combining with MBP-1 in ESCC, and may serve as a potential target for antitumor therapy in ESCC.