Benzopyrene diol epoxide‐induced transformed cells identify the significance of hsa_circ_0051488, a ERCC1‐derived circular RNA in pulmonary squamous cell carcinoma

• Published in: Molecular carcinogenesis Vol. 60; no. 10; pp. 684 - 701
• Main Authors: Xiao, Mingyang, Cui, Su, Zhang, Liang, Yu, Tao, Zhang, Guopei, Li, Liuli, Cai, Yuan, Jin, Cuihong, Yang, Jinghua, Wu, Shengwen, Li, Qingchang, Lu, Xiaobo
• Format: Journal Article
• Language: English
• Published: Austin Wiley Subscription Services, Inc 01.10.2021
• Subjects: Benzo(a)pyrene; Benzopyrene; Bioinformatics; Cell proliferation; Circular RNA; Cytoplasm; DNA damage; Epithelial cells; ERCC1 protein; Experiments; Lung cancer; Lung carcinoma; Phenotypes; Post-transcription; Pyrene; Squamous cell carcinoma; Transformed cells; Tumor suppressor genes; Tumorigenesis
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.23335

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.