Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Thorac Cancer. 2021 Aug;12(16):2258-2264. doi: 10.1111/1759-7714.14059. Epub 2021 Jul 8.
Circular RNAs (circRNAs) had been identified as a non-coding RNA associated with many types of cancer in recent years. However, the involvement of hsa_circ_0008274 in lung adenocarcinoma (LUAD) has not been explored. The aim of our research is to explore the biological mechanism and function of hsa_circ_0008274 in LUAD.
The hsa_circ_0008274, miR-578, and high mobility group AT-Hook 2 (HMGA2) mRNA expression levels were detected via qRT-PCR. Cell Counting Kit-8 (CCK-8) Transwell assay and wound healing assay were performed to measure the cell proliferation, invasion, and migration ability. Luciferase reporter and Western blotting experiments were performed to characterize the competing endogenous RNA (ceRNA) mechanism of hsa_circ_0008274.
Our findings determined that the expression of hsa_circ_0008274 in LUAD was significantly decreased. Cell experiments showed that overexpressed hsa_circ_0008274 could reduce the proliferation and invasion ability of LUAD cells. Moreover, miRNA-578 could identify as a miRNA sponge of hsa_circ_0008274. Overexpressed hsa_circ_0008274 reduced the proliferation and invasion of LUAD cells caused by miR-578 mimics. Increasing the expression of miR-578 can aggravate the proliferation and invasion of LUAD cells and block the inhibition of proliferation and invasion of LUAD cells mediated by overexpressed hsa_circ_0008274. Subsequent data indicate that HMGA2 of the tumor-promoting gene is the target gene of miR-578. The upregulation of HMGA2 partially reversed the tumor inhibitory effect of LUAD cells induced by overexpressed hsa_circ_0008274 or miR-578 mimics.
In summary, our data show that the overexpression of hsa_circ_0008274 repressed the proliferation and invasion of LUAD through downregulating miR-578 and activating HMGA2.
近年来，环状 RNA（circRNAs）已被鉴定为与多种类型癌症相关的非编码 RNA。然而，hsa_circ_0008274 在肺腺癌（LUAD）中的参与尚未得到探索。我们研究的目的是探讨 hsa_circ_0008274 在 LUAD 中的生物学机制和功能。
通过 qRT-PCR 检测 hsa_circ_0008274、miR-578 和高迁移率族 AT 盒 2（HMGA2）mRNA 的表达水平。通过细胞计数试剂盒-8（CCK-8）Transwell 测定和划痕愈合试验测定细胞增殖、侵袭和迁移能力。通过荧光素酶报告和 Western blot 实验研究 hsa_circ_0008274 的竞争性内源性 RNA（ceRNA）机制。
我们的研究结果表明，LUAD 中 hsa_circ_0008274 的表达明显降低。细胞实验表明，过表达 hsa_circ_0008274 可降低 LUAD 细胞的增殖和侵袭能力。此外，miR-578 可以作为 hsa_circ_0008274 的 miRNA 海绵。过表达 hsa_circ_0008274 降低了 miR-578 模拟物引起的 LUAD 细胞的增殖和侵袭。增加 miR-578 的表达会加重 LUAD 细胞的增殖和侵袭，并阻断过表达 hsa_circ_0008274 介导的 LUAD 细胞增殖和侵袭的抑制作用。随后的数据表明，肿瘤促进基因 HMGA2 是 miR-578 的靶基因。HMGA2 的上调部分逆转了过表达 hsa_circ_0008274 或 miR-578 模拟物诱导的 LUAD 细胞的肿瘤抑制作用。
综上所述，我们的数据表明，hsa_circ_0008274 的过表达通过下调 miR-578 并激活 HMGA2 抑制 LUAD 的增殖和侵袭。
