ERCC1 is 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 from ERCC1 can 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 certain ERCC1-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 of SATB2 gene, a lung cancer suppressor. Furthermore, our in silico experiments indicate that SATB2 can inhibit multiple tumor pathways and its expression positively correlated with the tumor suppressor gene CRMP1. These findings suggest a possible regulatory mechanism of hsa_circ_0051488 in LUSC, and that the newly discovered hsa_circ_0051488/miR-6717-5p/SATB2 axis may be a potential route for therapeutic intervention of LUSC.

中文翻译：

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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意义

ERCC1是一种修复 DNA 损伤的基因，其功能与致癌性诱导的肿瘤发生和铂类疗法的有效性有关。环状RNA（circRNA）是转录后调控的产物，对肺癌的发病机制具有多效性。我们的目标是确定源自ERCC1 的特定 circRNA可以调节参与肺癌发展的关键生物学过程。我们进行了生物信息学分析、体外实验和临床样本分析，以确定某个ERCC1的生物学特征在苯并[a]芘二醇环氧化物诱导的恶性转化细胞和肺癌细胞中，衍生的circRNA称为hsa_circ_0051488。已建立的转化细胞模型为分析该circRNA在肺上皮细胞恶性转化中的分子特征提供了理想的平台，支持hsa_circ_0051488在肺鳞状细胞癌（LUSC）的发病和生长中发挥作用。进一步分析表明，hsa_circ_0051488 的缺失促进了恶性表型细胞的增殖。大量实验证实 hsa_circ_0051488 存在于细胞质中并作为竞争性内源 RNA 发挥作用。特别是hsa_circ_0051488与mir-6717-5p结合，从而调节SATB2的表达基因，一种肺癌抑制基因。此外，我们的计算机模拟实验表明，SATB2可以抑制多种肿瘤通路，其表达与抑癌基因CRMP1呈正相关。这些发现提示了 LUSC 中 hsa_circ_0051488 可能的调控机制，新发现的 hsa_circ_0051488/miR-6717-5p/ SATB2轴可能是 LUSC 治疗干预的潜在途径。