Medical Oncology Department, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Cell Death Dis. 2021 Mar 24;12(4):313. doi: 10.1038/s41419-021-03601-2.
Lung adenocarcinoma (LUAD) has high incidence and mortality rates worldwide; however, its detailed molecular pathology remains unclear. Although circRNAs have gradually been identified as molecules that are differentially expressed in tumors and play key roles in tumor progression, their role in LUAD is poorly understood. Through microarray analysis, we obtained the circRNA expression profile of LUAD and found that circ-HMGA2 (hsa_circ_0027446), a novel RNA, is highly expressed in LUAD. The high expression of circ-HMGA2 was further verified in 36 paired LUAD and adjacent normal tissues. Functionally, circ-HMGA2 promoted LUAD cell metastasis in vitro and in vivo. The luciferase reporter assay and FISH results showed that circ-HMGA2 interacts with miR-1236-3p and that miR-1236-3p interacts with ZEB1. In addition, miR-1236-3p was expressed at low levels in LUAD, inhibited LUAD cell metastasis, and suppressed the function of circ-HMGA2. ZEB1 is an EMT-promoting transcription factor. The PCR and WB analysis results showed that circ-HMGA2 promotes both ZEB1 expression and EMT. MiR-1236-3p had the opposite effect, reversing the promotive effect of circ-HMGA2 on EMT. In summary, circ-HMGA2 promotes LUAD cell metastasis through the miR-1236-3p/EMT axis, indicating that it could be a therapeutic target in LUAD.
肺腺癌 (LUAD) 在全球范围内具有较高的发病率和死亡率；然而，其详细的分子病理学仍然不清楚。虽然 circRNAs 已逐渐被鉴定为在肿瘤中差异表达并在肿瘤进展中发挥关键作用的分子，但它们在 LUAD 中的作用仍知之甚少。通过微阵列分析，我们获得了 LUAD 的 circRNA 表达谱，发现一种新型 RNA circ-HMGA2 (hsa_circ_0027446) 在 LUAD 中高度表达。circ-HMGA2 的高表达在 36 对 LUAD 和相邻正常组织中进一步得到验证。功能上，circ-HMGA2 促进 LUAD 细胞体外和体内转移。荧光素酶报告基因检测和 FISH 结果表明，circ-HMGA2 与 miR-1236-3p 相互作用，而 miR-1236-3p 与 ZEB1 相互作用。此外，miR-1236-3p 在 LUAD 中表达水平较低，抑制 LUAD 细胞转移，并抑制 circ-HMGA2 的功能。ZEB1 是一种促进 EMT 的转录因子。PCR 和 WB 分析结果表明，circ-HMGA2 促进 ZEB1 表达和 EMT。miR-1236-3p 则有相反的作用，逆转了 circ-HMGA2 对 EMT 的促进作用。综上所述，circ-HMGA2 通过 miR-1236-3p/EMT 轴促进 LUAD 细胞转移，表明它可能成为 LUAD 的治疗靶点。
