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环状RNA circ_001621通过调控miR-199a-3p/GREM1轴在肺癌中发挥肿瘤促进作用。

Circular RNA circ_001621 acts as a tumor promoter in lung cancer by regulating the miR-199a-3p/GREM1 axis.

作者信息

Lei Jun, Qiao Song

机构信息

Department of Respiratory Medicine, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China.

Massage Department, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei, China.

出版信息

Arch Med Sci. 2024 Jun 28;20(3):876-886. doi: 10.5114/aoms/174052. eCollection 2024.

DOI:10.5114/aoms/174052
PMID:39050152
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11264106/
Abstract

INTRODUCTION

Investigating how circular RNAs (circRNAs) function during tumorigenesis may help uncover novel diagnostic markers for cancer treatment. The oncogenic role of circ_001621 has been verified in osteosarcoma, but its role in lung cancer has yet to be reported. This research is the first to investigate the circ_001621 expression and regulatory mechanism in lung cancer.

MATERIAL AND METHODS

RT-qPCR was performed to assess the circ_001621 expression levels in lung cancer cells and tissues. The influence of circ_001621 on the viability, invasive ability, and apoptosis of lung cancer cells was investigated through CCK-8, transwell, and caspase-3 activity experiments, respectively. A xenograft nude mouse model was designed to evaluate how circ_001621 functions . The RIP and luciferase reporter experiments confirmed the binding among circRNA, miRNA, and mRNA.

RESULTS

Circ_001621 was dramatically upregulated in lung cancer tissues and cells. Silencing circ_001621 in lung cancer cells reduced their viability and invasive ability but stimulated apoptosis. The nude mice experiment demonstrated that circ_001621 downregulation considerably stunted tumor growth . Additionally, circ_001621 could sponge miR-199a-3p. The inhibitor of miR-199a-3p improved the viability and invasion of cells while inhibiting apoptosis. Moreover, it offset the impact of circ_001621 on lung cancer cells. MiR-199a-3p was observed to target GREM1, and the downregulation of GREM1 could counteract miR-199a-3p-induced effects on lung cancer cells.

CONCLUSIONS

The circ_001621/miR-199a-3p/GREM1 axis exhibits an association with the development of lung cancer, suggesting its potential as a future therapeutic target for the disease.

摘要

引言

研究环状RNA（circRNA）在肿瘤发生过程中的作用机制，可能有助于发现癌症治疗的新型诊断标志物。circ_001621在骨肉瘤中的致癌作用已得到证实，但其在肺癌中的作用尚未见报道。本研究首次探讨circ_001621在肺癌中的表达及调控机制。

材料与方法

采用RT-qPCR检测肺癌细胞和组织中circ_001621的表达水平。分别通过CCK-8、Transwell和caspase-3活性实验，研究circ_001621对肺癌细胞活力、侵袭能力和凋亡的影响。构建裸鼠异种移植模型，评估circ_001621的功能。通过RNA免疫沉淀（RIP）和荧光素酶报告基因实验，证实circRNA、miRNA和mRNA之间的相互作用。

结果

circ_001621在肺癌组织和细胞中显著上调。沉默肺癌细胞中的circ_001621可降低其活力和侵袭能力，但促进细胞凋亡。裸鼠实验表明，下调circ_001621可显著抑制肿瘤生长。此外circ_001621可吸附miR-199a-3p。miR-199a-3p抑制剂可提高细胞活力和侵袭能力，同时抑制细胞凋亡。此外，它抵消了circ_001621对肺癌细胞的影响。研究发现miR-199a-3p靶向GREM1，下调GREM1可抵消miR-199a-3p对肺癌细胞的影响。

结论

circ_001621/miR-199a-3p/GREM1轴与肺癌的发生发展有关，提示其可能成为未来肺癌治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/db58c0799f22/AMS-20-3-174052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/70d42596d97a/AMS-20-3-174052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/029448c4b2ab/AMS-20-3-174052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/7a37936ad262/AMS-20-3-174052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/49a9895f3cac/AMS-20-3-174052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/e82446e94c91/AMS-20-3-174052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/db58c0799f22/AMS-20-3-174052-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/70d42596d97a/AMS-20-3-174052-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/029448c4b2ab/AMS-20-3-174052-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/7a37936ad262/AMS-20-3-174052-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/49a9895f3cac/AMS-20-3-174052-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/e82446e94c91/AMS-20-3-174052-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88fc/11264106/db58c0799f22/AMS-20-3-174052-g006.jpg

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