Department of Respiratory Medicine, The Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, P.R. China.
Department of Respiratory Medicine, The First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, P.R. China.
Mol Cancer Res. 2020 May;18(5):748-756. doi: 10.1158/1541-7786.MCR-19-0998. Epub 2020 Feb 14.
Previous studies indicated that circular RNAs (circRNA) played vital roles in the development of non-small cell lung cancer (NSCLC). Although hsa_circ_0014130 might be a potential NSCLC biomarker, its function in NSCLC remains unknown. Thus, this study aimed to investigate the role of hsa_circ_0014130 in the progression of NSCLC. The levels of hsa_circ_0014130 in NSCLC tissues and adjacent normal tissues were determined by qRT-PCR. In addition, the expressions of Bcl-2 and cleaved caspase-3 in A549 cells were detected with Western blot analysis. Meanwhile, the dual luciferase reporter system assay was used to determine the interaction of hsa_circ_0014130 and miR-136-5p or Bcl-2 and miR-136-5p in NSCLC, respectively. The level of hsa_circ_0014130 was significantly upregulated in NSCLC tissues. Downregulation of hsa_circ_0014130 markedly inhibited the proliferation and invasion of A549 cells via inducing apoptosis. In addition, downregulation of hsa_circ_0014130 inhibited the tumorigenesis of subcutaneous A549 xenograft in mice . Meanwhile, mechanistic analysis indicated that downregulation of hsa_circ_0014130 decreased the expression of miR-136-5p-targeted gene via acting as a competitive "sponge" of miR-136-5p. In this study, we found that hsa_circ_0014130 was upregulated in NSCLC tissues. In addition, hsa_circ_0014130 functions as a tumor promoter in NSCLC to promote tumor growth through upregulating Bcl-2 partially via "sponging" miR-136-5p. IMPLICATIONS: In conclusion, hsa_circ_0014130 might function as a prognostic factor for patients with NSCLC and might be a therapeutic target for the treatment of NSCLC in future.
先前的研究表明，环状 RNA（circRNA）在非小细胞肺癌（NSCLC）的发展中发挥着重要作用。虽然 hsa_circ_0014130 可能是一种潜在的 NSCLC 生物标志物，但它在 NSCLC 中的作用尚不清楚。因此，本研究旨在探讨 hsa_circ_0014130 在 NSCLC 进展中的作用。通过 qRT-PCR 测定 NSCLC 组织和相邻正常组织中的 hsa_circ_0014130 水平。此外，通过 Western blot 分析检测 A549 细胞中 Bcl-2 和 cleaved caspase-3 的表达。同时，分别使用双荧光素酶报告系统测定 NSCLC 中 hsa_circ_0014130 与 miR-136-5p 或 Bcl-2 与 miR-136-5p 的相互作用。结果显示，hsa_circ_0014130 在 NSCLC 组织中显著上调。下调 hsa_circ_0014130 显著通过诱导细胞凋亡抑制 A549 细胞的增殖和侵袭。此外，下调 hsa_circ_0014130 抑制了小鼠皮下 A549 异种移植瘤的肿瘤发生。同时，机制分析表明，下调 hsa_circ_0014130 通过作为 miR-136-5p 的竞争性“海绵”降低了 miR-136-5p 靶向基因的表达。在本研究中，我们发现 hsa_circ_0014130 在 NSCLC 组织中上调。此外，hsa_circ_0014130 作为 NSCLC 中的肿瘤促进因子，通过部分上调 Bcl-2 通过“海绵”miR-136-5p 促进肿瘤生长。结论：hsa_circ_0014130 可能作为 NSCLC 患者的预后因素，并可能成为未来 NSCLC 治疗的治疗靶点。
