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环状 RNA hsa_circ_0102231 通过海绵吸附 miR-145 来上调 RBBP4 的表达,从而促进非小细胞肺癌细胞的增殖。

Circular RNA hsa_circ_0102231 sponges miR-145 to promote non-small cell lung cancer cell proliferation by up-regulating the expression of RBBP4.

机构信息

Department of Respiratory Medicine, Heze Municipal Hospital, 2888 Caozhou Road, Heze, Shandong, 274000, People's Republic of China.

出版信息

J Biochem. 2021 Feb 6;169(1):65-73. doi: 10.1093/jb/mvaa093.

DOI:10.1093/jb/mvaa093
PMID:33084863
Abstract

Circular RNAs (circRNAs) are important regulators in various cancers. Previous studies have found that hsa_circ_0102231 is an oncogene in lung adenocarcinoma. Here, we investigated its mechanism in the development of non-small cell lung cancer (NSCLC). We detected the levels of hsa_circ_0102231 in five NSCLC cell lines and one normal bronchial epithelium cell line. The interaction between hsa_circ_0102231 and miR-145 was predicted and confirmed by pull-down and luciferase assays. The nuclear mass separation assay and fluorescence in situ hybridization were used to detect the distribution of hsa_circ_0102231. Cell Counting Kit-8 and Transwell assays were used to assess the cell proliferative and invasive ability. Western blot and RT-qPCR, respectively, detected the protein and mRNA levels of RBBP4. The RBBP4 promoter activity was detected with a luciferase assay. We found that hsa_circ_0102231 level was higher in NSCLC cells. hsa_circ_0102231 is mainly localized to the cytoplasm. hsa_circ_0102231 promotes NSCLC cell proliferation and invasion by sponge for miR-145. miR-145 significantly decreases the RBBP4 promoter activity, and its mRNA and protein levels. RBBP4 is an oncogene to promote proliferation and invasion ability. Our findings suggest that hsa_circ_0102231 promotes proliferation and invasion by mediating the miR-145/RBBP4 axis in NSCLC, indicating that it might be a potential target for NSCLC treatment.

摘要

环状 RNA(circRNAs)是各种癌症中的重要调节因子。先前的研究发现 hsa_circ_0102231 是肺腺癌中的一个癌基因。在这里,我们研究了其在非小细胞肺癌(NSCLC)发展中的机制。我们检测了 5 种 NSCLC 细胞系和 1 种正常支气管上皮细胞系中的 hsa_circ_0102231 水平。通过下拉和荧光素酶测定预测并证实了 hsa_circ_0102231 与 miR-145 的相互作用。核质量分离测定和荧光原位杂交用于检测 hsa_circ_0102231 的分布。细胞计数试剂盒-8 和 Transwell 测定用于评估细胞增殖和侵袭能力。Western blot 和 RT-qPCR 分别检测 RBBP4 的蛋白和 mRNA 水平。荧光素酶测定检测 RBBP4 启动子活性。我们发现 hsa_circ_0102231 在 NSCLC 细胞中的水平较高。hsa_circ_0102231 主要定位于细胞质。hsa_circ_0102231 通过海绵吸附 miR-145 促进 NSCLC 细胞增殖和侵袭。miR-145 显著降低 RBBP4 启动子活性及其 mRNA 和蛋白水平。RBBP4 是促进增殖和侵袭能力的癌基因。我们的研究结果表明,hsa_circ_0102231 通过调节 NSCLC 中的 miR-145/RBBP4 轴促进增殖和侵袭,表明其可能是 NSCLC 治疗的潜在靶点。

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