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环状 RNA 结合蛋白 1 通过作为 miR-615-5p 的 ceRNA 调节 DDR2 表达促进 T 细胞淋巴母细胞淋巴瘤的进展。

Circ-LAMP1 promotes T-cell lymphoblastic lymphoma progression via acting as a ceRNA for miR-615-5p to regulate DDR2 expression.

机构信息

Department of Pediatric, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China.

Department of Respiratory, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161000, China.

出版信息

Gene. 2019 Jun 15;701:146-151. doi: 10.1016/j.gene.2019.03.052. Epub 2019 Mar 25.

Abstract

Circular RNAs (circRNAs) act as pivotal functions in tumor progression. Nevertheless, the functions and mechanism of circRNAs in T-cell lymphoblastic lymphoma (T-LBL) remain unclear. In this work, we first screened the differentially expressed circRNAs between T-LBL tissues and normal infantile thymus and circ-LAMP1 was identified the highest expressed circRNA in cancerous tissues. qRT-PCR further verified its upregulation in T-LBL tissues and cell lines. Cell counting kit-8 (CCK-8) experiment proved the cell proliferation-promoting role of circ-LAMP1. This effect is partially dependent on its inhibition on cell apoptosis proved by flow cytometric assay. Dual-luciferase reporter system further identified that miR-615-5p could be sponged by circ-LAMP1 and discoidin domain receptor tyrosine kinase 2 (DDR2) 3'-UTR is the direct target of miR-615-5p. Rescue assays demonstrated that the biological function of circ-LAMP1 is partly attributed to the modulation of miR-615-5p/DDR2 signaling. In summary, these findings documented that circ-LAMP1 might be an oncogene in T-LBL, which might be useful in developing promising therapies for T-LBL.

摘要

环形 RNA(circRNAs)在肿瘤进展中发挥关键作用。然而,circRNAs 在 T 细胞淋巴母细胞淋巴瘤(T-LBL)中的功能和机制仍不清楚。在这项工作中,我们首先筛选了 T-LBL 组织与正常婴儿胸腺之间差异表达的 circRNAs,发现 circ-LAMP1 在癌组织中表达最高。qRT-PCR 进一步验证了其在 T-LBL 组织和细胞系中的上调。细胞计数试剂盒-8(CCK-8)实验证明了 circ-LAMP1 促进细胞增殖的作用。通过流式细胞术实验证明,这种作用部分依赖于对细胞凋亡的抑制。双荧光素酶报告系统进一步证实,circ-LAMP1 可以吸附 miR-615-5p,而 discoidin 结构域受体酪氨酸激酶 2(DDR2)3'-UTR 是 miR-615-5p 的直接靶标。挽救实验表明,circ-LAMP1 的生物学功能部分归因于 miR-615-5p/DDR2 信号的调节。总之,这些发现表明 circ-LAMP1 可能是 T-LBL 的癌基因,这可能有助于开发针对 T-LBL 的有前途的治疗方法。

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