Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.
Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.
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DOI：
10.1016/j.tranon.2023.101635
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发表时间：
2023-04
影响因子：
5
通讯作者：
Zhou, Qiong
中科院分区：
文献类型：
--
作者：
Wang, Zi-Hao;Ye, Lin-Lin;Xiang, Xuan;Wei, Xiao-Shan;Niu, Yi-Ran;Peng, Wen-Bei;Zhang, Si-Yu;Zhang, Pei;Xue, Qian-Qian;Wang, Hao-Lei;Du, Yi-Heng;Liu, Yao;Ai, Jia-Qi;Zhou, Qiong
FBXO7环状RNA过表达抑制了NSCLC细胞的增殖。环状RNA环FBXO7直接抑制miR-296-3p作为CerNA。KLF15直接与CDKN1A基因启动子结合，促进其表达。小鼠同源环状RNA CircFbxo7过表达也抑制了肿瘤生长。新发现的FBXO7/miR-296-3p/KLF15/CDKN1A轴调控NSCLC细胞增殖。越来越多的证据表明，环状RNA(CircRNAs)在多种癌症中发挥重要作用。人血清白蛋白_CIRC_0008832(FbxO7)是从人类F-box Only Protein 7(Fbxo7)的第二外显子中产生的一种CircRNA。小鼠CircFbxo7是由小鼠F-box Only Protein 7(Fbxo7)的第二外显子产生的CircRNA。非小细胞肺癌(NSCLC)中人FbxO7基因和小鼠Fbxo7基因的作用尚未见报道。用实时荧光定量聚合酶链式反应检测CircFBXO7基因的表达。采用生存分析的方法探讨CircFBXO7的表达与非小细胞肺癌患者预后的关系。将重组表达载体导入肺癌细胞系。对细胞增殖、细胞周期和肿瘤形成进行评估，以评估CircFBXO7的作用。采用荧光原位杂交法对人和小鼠肺癌细胞中CircFbxo7和CircFbxo7进行定位。通过荧光素酶报告实验，进一步证实了CircFBXO7与microRNA的关系。在本研究中，我们发现大约FBXO7在非小细胞肺癌组织和细胞系中表达下调。周围FBXO7高表达的非小细胞肺癌患者总生存期延长。过表达CircFBXO7在体外和体内均可抑制细胞增殖。在机制上，我们证明了FBXO7左右上调了miR-296-3p靶基因Krüppel-like factor15(KLF15)的表达，KLF15反式激活了CDKN1A的表达。CircFBXO7通过FBXO7/miR-296-3p/KLF15/CDKN1A轴发挥肿瘤抑制作用，可能成为NSCLC潜在的生物标志物和治疗靶点。
Circular RNA circFBXO7 overexpression suppressed NSCLC cells proliferation. Circular RNA circFBXO7 directly inhibited miR-296-3p as a ceRNA. KLF15 bound to the promoter of CDKN1A gene directly and promoted its expression. Mouse homologous circular RNA circFbxo7 overexpression also suppressed tumor growth. The novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis regulated NSCLC cell proliferation. Accumulating evidence indicates that circular RNAs (circRNAs) play important roles in various cancers. Hsa_circ_0008832 (circFBXO7) is a circRNA generated from the second exon of the human F-box only protein 7 (FBXO7). Mouse circFbxo7 is a circRNA generated from the second exon of mouse F-box only protein 7 (Fbxo7). The role of human circFBXO7 and mouse circFbxo7 in non-small cell lung cancer (NSCLC) has not been reported. The expression of circFBXO7 was measured by quantitative real-time PCR. Survival analysis was performed to explore the association between the expression of circFBXO7 and the prognosis of patients with NSCLC. Lung cancer cell lines were transfected with plasmids. Cell proliferation, cell cycle, and tumorigenesis were evaluated to assess the effects of circFBXO7. Fluorescence in situ hybridization assay was used to identify the location of circFBXO7 and circFbxo7 in human and mouse lung cancer cells. Luciferase reporter assay was conducted to confirm the relationship between circFBXO7 and microRNA. In this study, we found that circFBXO7 was downregulated in NSCLC tissues and cell lines. NSCLC patients with high circFBXO7 expression had prolonged overall survival. Overexpression of circFBXO7 inhibited cell proliferation both in vitro and in vivo. Mechanistically, we demonstrated that circFBXO7 upregulated the expression of miR-296-3p target gene Krüppel-like factor 15 (KLF15) and KLF15 transactivated the expression of CDKN1A. CircFBXO7 acts as a tumor suppressor by a novel circFBXO7/miR-296-3p/KLF15/CDKN1A axis, which may serve as a potential biomarker and therapeutic target for NSCLC.
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影响因子：
8.4
作者：
Bai, Yifeng;Liao, Hongzhan;Guo, Linlang
通讯作者：
Guo, Linlang
circTP63 作为 ceRNA 通过上调 FOXM1 促进肺鳞状细胞癌进展
影响因子：
16.6
作者：
Cheng, Zhuoan;Yu, Chengtao;Qin, Wenxin
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DOI：
10.1016/j.omtn.2020.11.012
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
Liang Y;Wang H;Chen B;Mao Q;Xia W;Zhang T;Song X;Zhang Z;Xu L;Dong G;Jiang F
通讯作者：
Jiang F
影响因子：
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作者：
Hu L;Ai J;Long H;Liu W;Wang X;Zuo Y;Li Y;Wu Q;Deng Y
通讯作者：
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影响因子：
5
作者：
Mortoglou M;Tabin ZK;Arisan ED;Kocher HM;Uysal-Onganer P
通讯作者：
Uysal-Onganer P