hsa_circ_0003176 Suppresses the Progression of Non-Small-Cell Lung Cancer via Regulating miR-182-5p/RBM5 Axis

Abstract

Background. Non-small-cell lung cancer (NSCLC) is one of the major diseases that threaten human health, and there is still no fundamental treatment method. Emerging evidences suggested that circRNAs might be an effective target to treatment NSCLC. However, the roles and detailed mechanisms of hsa_circ_0003176 in NSCLC still not clear. Methods. hsa_circ_0003176 was identified from GSE101684 and GSE112214 datasets of Gene Expression Omnibus (GEO) database. The expression of hsa_circ_0003176 was detected by RT-qPCR in NSCLC tissues, paired adjacent nontumor tissues, and cell lines. RNA fluorescence in situ hybridization and nuclear and cytoplasmic RNA fractionation analysis was used to detect the subcellular localization of hsa_circ_0003176 in H1299 and A549 cells. Dual-luciferase reporter and RNA pull-down assay were used to confirm the regulatory of miR-182-5p to hsa_circ_0003176 and RBM5. The roles of hsa_circ_0003176 in NSCLC progression was evaluated both in vitro by CCK-8 assay, colony formation assay, wound-healing assay, and matrigel transwell assay and in vivo by the subcutaneous xenograft nude mouse experiment and lung metastasis nude mouse experiment. In addition, RNA pull down and luciferase reporter assays were carried out to investigate the interaction between hsa_circ_0003176 or RBM5 and miR-182-5p. Results. Our results indicated that hsa_circ_0003176 showed typical characteristic of circRNAs, which was downregulated in both NSCLC tissues and cell lines. Functionally, overexpression of hsa_circ_0003176 suppressed the proliferation, migration, and invasion of NSCLC cells in vitro and inhibited NSCLC growth and metastasis in vivo. Furthermore, we found that hsa_circ_0003176 acts as sponge of miR-182-5p to regulate RBM5 expression. Further, in vitro rescue experiments demonstrated that hsa_circ_0003176 suppressed the proliferation, migration, and invasion of NSCLC cells by regulating miR-182-5p/RBM5 axis. Conclusion. We demonstrated that hsa_circ_0003176 suppressed the NSCLC progression via regulating miR-182-5p/RBM5 axis. These data indicated that hsa_circ_0003176 might be a novel molecular target for NSCLC treatment.

Nucleus‐localized circSLC39A5 suppresses hepatocellular carcinoma development by binding to STAT1 to regulate TDG transcription

“…The function of circRNAs is related to their sequence, stability, post‐transcriptional modification, secondary structure, and the cellular sites where they accumulate 54 . Many studies have reported that circRNAs are localized in the cytoplasm so that they can absorb miRNA 55,56 . Additionally, some circRNAs are localized in the nucleus; for instance, circ‐HuR, which interacts with CNBP to inhibit its binding to HuR promoters, leading to HuR downregulation 57 .…”

“… 54 Many studies have reported that circRNAs are localized in the cytoplasm so that they can absorb miRNA. 55 , 56 Additionally, some circRNAs are localized in the nucleus; for instance, circ‐HuR, which interacts with CNBP to inhibit its binding to HuR promoters, leading to HuR downregulation. 57 An intronic circRNA, circ‐CTNNB1, can bind to DDX3, promote its physical interaction with the transcription factor YY1 and regulate transcription.…”

Exosomal circular RNA: a signature for lung cancer progression

“…Recently, in both NSCLC tissues and cell lines, hsa_circ_0003176 had the typical characteristics of circRNAs, which were downregulated. Functionally, hsa_circ_0003176 was overexpressed, which prevented NSCLC cells from proliferating, invading other cells, and growing both in vitro and in vivo [ 107 ]. These findings might improve our understanding of the molecular processes behind the development of NSCLC into a malignant state.…”

Circ_0087378 intensifies the malignant behavior of non-small cell lung cancer cells in vitro by facilitating DDR1 via sponging miR-199a-5p

“…For example, circular pleiotrophin (circPTN) and circRNA C190 have been proven to be oncogenic for NSCLC ( 13 , 14 ). Conversely, circ_0002346 and circ_0003176 have been identified to be tumor suppressors for NSCLC ( 15 , 16 ). However, the expression and function of circ_0087378 has never been researched currently.…”