Benzo[a]pyrene diol epoxide-induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1-derived circular RNA in pulmonary squamous cell carcinoma.

Benzo[a]pyrene diol epoxide-induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1-derived circular RNA in pulmonary squamous cell carcinoma.
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苯并[a]芘二醇环氧化物诱导的转化细胞鉴定了 hsa_circ_0051488(一种 ERCC1 衍生的环状 RNA)在肺鳞状细胞癌中的重要性。

DOI:
10.1002/mc.23335
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发表时间:
2021
影响因子:
4.6
通讯作者:
Lu Xiaobo
Lu Xiaobo
中科院分区:
医学2区
文献类型:
--
作者:
Xiao Mingyang;Cui Su;Zhang Liang;Yu Tao;Zhang Guopei;Li Liuli;Cai Yuan;Jin Cuihong;Yang Jinghua;Wu Shengwen;Li Qingchang;Lu Xiaobo

文献摘要

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ERCC1is a gene for repairing DNA damage whose function is related to carcinogenic‐induced tumorigenesis and the effectiveness of platinum therapies. Circular RNAs (circRNAs) are products of posttranscriptional regulation with pleiotropic effects on the pathogenesis of lung cancer. We aim to identify that specific circRNAs derived fromERCC1can regulate key biological processes involved in the development of lung cancer. We performed bioinformatics analysis, in vitro experiments, and analyzed clinical samples, to determine the biological features of a certainERCC1‐derived circRNA termed as hsa_circ_0051488 in benzo[a]pyrene diol epoxide‐induced malignant transformed cell and lung cancer cell. The well‐established model of transformed cells provided an ideal platform for analyzing the molecular characteristics of this circRNA in the malignant transformation of lung epithelial cell, which supports that hsa_circ_0051488 functions in the onset and growth of lung squamous cell carcinoma (LUSC). Further analysis indicates that the absence of hsa_circ_0051488 promoted the proliferation of cells with the malignant phenotype. Extensive experiments confirm that hsa_circ_0051488 is present in the cytoplasm and functioned as a competing endogenous RNA. In particular, hsa_circ_0051488 binds to mir‐6717‐5p, thereby modulating the expression ofSATB2gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate thatSATB2can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor geneCRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR‐6717‐5p/SATB2axis may be a potential route for therapeutic intervention of LUSC.