Dataset Information

Hsa_circ_0058357 acts as a ceRNA to promote non‑small cell lung cancer progression via the hsa‑miR‑24‑3p/AVL9 axis.

ABSTRACT: Abnormal circular RNAs (circRNAs) are associated with biological processes in cancer; however, the function of circRNAs remains largely unknown in non‑small cell lung cancer (NSCLC). The present study aimed to investigate the role of hsa_circ_0058357 on the progression of NSCLC. Cell proliferation, migration and apoptosis were determined using Cell Counting Kit‑8, Transwell and flow cytometry assays, respectively. Gene [circRNA and microRNA (miR)] and protein expression levels were determined via reverse transcription‑quantitative PCR and immunoblotting. A luciferase assay was employed to detect the binding of miR‑24‑3p with AVL9 cell migration associated (AVL9), while a cancer xenograft model was established to evaluate cancer growth in vivo. The results demonstrated that hsa_circ_0058357 was highly expressed in human NSCLC tissues and NSCLC cells compared with para‑cancerous tissues and human bronchial epithelial (HBE) cells, respectively. Knockdown of hsa_circ_0058357 significantly suppressed cell viability, migration and tumor growth, while it promoted apoptosis in NSCLC cells. As a competing endogenous RNA, hsa_circ_0058357 knockdown contributed to the increase of miR‑24‑3p expression in NSCLC cells. Of note, overexpression of miR‑24‑3p markedly abolished the exogenous hsa_circ_0058357‑induced excessive proliferation, migration and apoptosis resistance of NSCLC cells. Mechanistically, as a signaling molecule in late secretory pathway, AVL9 was also expressed at a high level in NSCLC tissues and cells, which could be directly suppressed by miR‑24‑3p. In the tumor tissues, along with growth inhibition, hsa_circ_0058357 knockdown also mediated the elevation of miR‑24‑3p and the reduction of AVL9. Thus, it was suggested that hsa_circ_0058357 may be a crucial regulation factor in NSCLC by sponging hsa‑miR‑24‑3p, leading to a decrease in miR‑24‑3p expression, and subsequent increase in AVL9 expression. Therefore, hsa_circ_0058357 may serve as a potential target for diagnosis and gene therapy for NSCLC.

SUBMITTER: Wei D

PROVIDER: S-EPMC8097761 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThough circular RNAs (circRNAs) are the key regulators in tumor carcinogenesis, they remain largely unexplored in hepatocellular carcinoma (HCC).MethodsThe expression of RanGAP1-derived circRNAs (circ_0063531, circ_0063534, circ_0063513, circ_0063518, circ_0063507, circ_0063723) were evaluated in eight paired HCC and normal tissues, and the correlation between circRanGAP1 (circ_0063531) expression and clinicopathological characteristics in 40 HCC patients was determined. The association between miR-27b-3p and circRanGAP1 or NRAS was predicted using bioinformatics analysis. The expression of circRanGAP1, miR-27b-3p, and NRAS were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The potential oncogenic role of circ-RanGAP1 was assessed using CCK-8, colony formation, transwell assays in vitro, subcutaneous tumor mouse model, vein tail metastatic model, and orthotopically implanted intrahepatic HCC model in vivo. Luciferase reporter and RNA immunoprecipitation (RIP) assays were used to explore the binding site between miR-27b-3p and circ-RanGAP1 or NRAS. Protein expression was detected using western blotting. The localization of miR-27b-3p and circ-RanGAP1 was investigated using fluorescence in situ hybridization (FISH). The level of immune infiltration was assessed by bioinformatics analysis, flow cytometry, and orthotopically implanted intrahepatic HCC models.ResultsHere, we found elevated circRanGAP1 in the cells and clinical tissues of patients with HCC. Increased circRanGAP1 levels are associated with enlarged tumors and the advanced stage of TNM. CircRanGAP1 promotes the growth, migration, and HCC cell invasion, concurrently with the growth and metastasis of tumors in-vivo. Moreover, circRanGAP1 is mainly located inside the cytoplasm. Mechanistically, circRanGAP1 as an oncogene promotes HCC progression by miR-27b-3p/NRAS/ERK axis, furthermore, affects the infiltration level of tumor-associated macrophages probably by sponging miR-27b-3p. Immune infiltration analysis shows that NRAS is positively correlated with the levels of CD68+ tumor-associated macrophages in HCC samples and that NRAS and CD68 are related to the poor outcome of HCC.ConclusionThese results reveal that circRanGAP1 is a HCC oncogene that function by the miR-27b-3p/NRAS/ERK axis and regulates the infiltration levels of tumor-associated macrophages by sponging miR-27b-3p. Therefore, circRANGAP1/ NRAS axis may be an important potential treatment target against HCC.

Dataset Information

Hsa_circ_0058357 acts as a ceRNA to promote non‑small cell lung cancer progression via the hsa‑miR‑24‑3p/AVL9 axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets