Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences; Department of Thoracic Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Mol Cancer. 2018 Sep 20;17(1):138. doi: 10.1186/s12943-018-0887-9.
Oncogenic fusion gene Echinoderm Microtubule-associated protein-Like 4-Anaplastic Lymphoma Kinase (EML4-ALK) contributes to tumorigenesis of a subset of non-small cell lung cancer (NSCLC). Recently, we demonstrated that F-circEA-4a, a tumor-promoting circular RNA (circRNA) generated from the back-splicing of EML4-ALK variant 3b (v3b), is a novel liquid biopsy biomarker for NSCLC. However, circRNAs produced from EML4-ALK gene and their roles in NSCLC are not well-characterized. Here, we identify another EML4-ALK-v3b-derived circRNA, F-circEA-2a, harboring "AA" (rather than "AAAA" in F-circEA-4a) motif at the junction site. F-circEA-2a mainly locates in the cytoplasm and promotes cell migration and invasion, but has little effect on cell proliferation. Moreover, F-circEA-2a exists in tumor, but not in the plasma of NSCLC patients with EML4-ALK fusion gene, further supporting the significant diagnostic value of F-circEA-4a for EML4-ALK-positive NSCLC. This work finds a novel oncogenic circRNA generated from EML4-ALK fusion gene, highlighting the pivotal role of circRNA in EML4-ALK-positive NSCLC development.
棘皮动物微管相关蛋白样 4-间变性淋巴瘤激酶（EML4-ALK）致癌融合基因导致一部分非小细胞肺癌（NSCLC）的肿瘤发生。最近，我们证明了 F-circEA-4a，一种来源于 EML4-ALK 变体 3b（v3b）反向剪接的促肿瘤环状 RNA（circRNA），是 NSCLC 的一种新型液体活检生物标志物。然而，源自 EML4-ALK 基因的 circRNAs 及其在 NSCLC 中的作用尚未得到很好的描述。在这里，我们鉴定了另一种 EML4-ALK-v3b 衍生的 circRNA，F-circEA-2a，其连接位点具有“AA”（而不是 F-circEA-4a 中的“AAAA”）基序。F-circEA-2a 主要位于细胞质中，促进细胞迁移和侵袭，但对细胞增殖几乎没有影响。此外，F-circEA-2a 存在于肿瘤中，但不存在于具有 EML4-ALK 融合基因的 NSCLC 患者的血浆中，进一步支持 F-circEA-4a 对 EML4-ALK 阳性 NSCLC 的显著诊断价值。这项工作发现了一种源自 EML4-ALK 融合基因的新型致癌 circRNA，强调了 circRNA 在 EML4-ALK 阳性 NSCLC 发展中的关键作用。
