Laboratory of Pathology, Hebei Cancer Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Mol Cancer Res. 2021 Sep;19(9):1465-1475. doi: 10.1158/1541-7786.MCR-20-1025. Epub 2021 May 20.
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-β1-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. IMPLICATIONS: LINC00239 may function as an oncogenic lncRNA in ESCC through the LINC00239/MBP-1/c-Myc axis to activate EMT process.
越来越多的证据表明，长非编码 RNA（lncRNA）在肿瘤的进展中发挥着重要作用，包括食管鳞状细胞癌（ESCC）。LINC00239 已被报道为多种癌症的癌基因，但其在 ESCC 中的具体作用尚不清楚。在本研究中，我们检测了 LINC00239 在 ESCC 标本和细胞中的表达和功能作用，并探讨了其分子机制。LINC00239 在 ESCC 组织和细胞中高表达，与 ESCC 患者的预后不良相关。LINC00239 过表达的 ESCC 细胞的增殖、转移和侵袭能力以及上皮-间充质转化（EMT）过程均增强。TGF-β1 处理的 ESCC 细胞中 LINC00239 上调。此外，发现 LINC00239 直接与转录因子 c-Myc 启动子结合蛋白-1（MBP-1）结合。MBP-1 被检测到抑制 ESCC 中 c-Myc 的转录。此外，LINC00239 可以通过影响 MBP-1 与 c-Myc 启动子的结合能力来激活 c-Myc 的转录。这些数据表明，LINC00239 可能通过与 MBP-1 竞争结合在 ESCC 中激活 c-Myc 转录，从而作为 ESCC 中抗肿瘤治疗的潜在靶点。意义：LINC00239 可能通过 LINC00239/MBP-1/c-Myc 轴作为致癌 lncRNA 在 ESCC 中发挥作用，激活 EMT 过程。
