Dataset Information

Circular RNA circ_0000517 Facilitates The Growth and Metastasis of Non-Small Cell Lung Cancer by Sponging miR-326/miR-330-5p.

ABSTRACT:

Objective

There is growing evidence showing that circular RNAs (circRNAs) are crucial regulators in modulating the biological behavior of tumors. This work is aimed to probe the role of circ_0000517 in non-small cell lung cancer (NSCLC) and to elucidate its mechanism of action.

Materials and methods

In this experimental study, the differentially expressed circRNAs in NSCLC were screened using the GEO database (GSE158695). Circ_0000517, miR-326, miR-330-5p, and MMP2 expression levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) analysis and Western blot. The proliferation, apoptosis, migration, and invasion of NSCLC cells were detected by CCK-8, flow cytometry, and transwell assays. RNA immunoprecipitation (RIP), RNA pull-down, and dual-luciferase reporter gene assays were performed to clarify the association between the circ_0000517 and miR-326/miR-330-5p.

Results

Circ_0000517 was shown to be up-regulated in NSCLC tissues and cell lines. The up-regulation of circ_0000517 is closely associated with advanced clinical stage of cancer, lymph node metastasis, and poor prognosis in NSCLC patients. Circ_0000517 knockdown impeded the proliferation, migration, and invasion of NSCLC cells and enhanced their apoptosis. Mechanistically, circ_0000517 was demonstrated to up-regulate MMP2 expression via decoying miR-326 and miR-330-5p to facilitate the malignant biological behaviors of NSCLC cells.

Conclusion

This work reveals that circ_0000517 is implicated in NSCLC cell growth and metastasis through the modulation of miR-326/miR-330-5p/MMP2, providing novel insights into the role of circRNAs in NSCLC progression.

SUBMITTER: Tan Q

PROVIDER: S-EPMC8588814 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundLung adenocarcinoma (LUAD) is currently the leading cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) play key roles in tumor occurrence and development as crucial cancer regulators. The present study aimed to explore the molecular mechanism and regulatory network of Linc00511 in LUAD and to identify new potential therapeutic targets for LUAD.MethodsReal-time quantitative polymerase chain reaction (RT-qPCR) was performed to determine the relative Linc00511 levels in LUAD tissues and cells. The proliferation, apoptosis, migration, and invasion abilities of LUAD cells were assessed by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, flow cytometry, and a Transwell assay. Changes in hsa_miR-126-5p, hsa_miR-218-5p, and COL1A1 expression were analyzed using western blotting and RT-qPCR. Targeted binding between miR-126-5p/miR-218-5p and Linc00511 or COL1A1 was verified with a luciferase reporter system and confirmed by an RNA pulldown assay. The participation of the PI3K/AKT signaling pathway was confirmed via western blotting. Xenograft animal experiments were performed to detect the impact of Linc00511 on LUAD tumor growth in vivo.ResultsIn the present work, we observed that Linc00511 was upregulated in LUAD tissues and cells. Loss/gain-of-function experiments indicated that knockdown of Linc00511 significantly inhibited LUAD cell proliferation, migration and invasion and promoted LUAD cell apoptosis, whereas overexpression of Linc00511 showed the opposite effects. In addition, we determined that Linc00511 promoted COL1A1-mediated cell proliferation and cell motility by sponging miR-126-5p and miR-218-5p. Moreover, Linc00511 activated the PI3K/AKT signaling pathway through upregulation of COL1A1. Finally, silencing of Linc00511 inhibited LUAD tumor growth in vivo.ConclusionsLinc00511 acts as a competing endogenous RNA to regulate COL1A1 by targeting miR-126-5p and miR-218-5p, thereby promoting the proliferation and invasion of LUAD cells.