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

Abstract

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.

Identification of a Novel Survival-Related circRNA–miRNA–mRNA Regulatory Network Related to Immune Infiltration in Liver Hepatocellular Carcinoma

“…In this study, we performed differential expression analysis on the GSE164803 dataset in the GEO database, identified seven circRNAs with significantly upregulated expression in liver cancer tissues compared with normal liver tissues and verified them in LIHC clinical specimens by qRT–PCR. Among them, one circRNA was previously reported to be closely related to cancer: hsa_circ_0051488 sponges miR-6717–5p, thereby regulating the expression of SATB2, which plays a vital role in lung squamous cell carcinoma ( Xiao et al, 2021 ). However, there is no research focusing on the significance of the other circRNAs, and they are worthy of further study.…”

Landscape of circular RNAs in different types of lung cancer and an emerging role in therapeutic resistance (Review)

“…A xenograft tumor growth assay suggested that it acted as a tumor promoter in LUSC and influenced LUSC proliferation and invasion via the miR-136-5p/Rho associated coiled-coil containing protein kinase 1 (ROCK1) axis ( 87 ). In addition, hsa_circ_0051488 expression in cancer tissues was inversely correlated with tumor diameter, lymphatic metastasis and TNM stage ( 88 ). Further experiments indicated that circ0051488 may promote LUSC progression through the miR6715/special AT-rich sequence-binding protein 2 (SATB2) axis, suggesting that circ0051488/miR6715/SATB2 may be a potential pathway for LUSC therapeutic intervention ( 88 ).…”

“…In addition, hsa_circ_0051488 expression in cancer tissues was inversely correlated with tumor diameter, lymphatic metastasis and TNM stage ( 88 ). Further experiments indicated that circ0051488 may promote LUSC progression through the miR6715/special AT-rich sequence-binding protein 2 (SATB2) axis, suggesting that circ0051488/miR6715/SATB2 may be a potential pathway for LUSC therapeutic intervention ( 88 ).…”