Hypoxic Tumor-derived Exosomal Circular RNA SETDB1 Promotes Invasive Growth and EMT Via the MiR-7/Sp1 Axis in Lung Adenocarcinoma

Overview

Journal Mol Ther Nucleic Acids

Publisher Cell Press

Date 2021 Feb 22

PMID 33614250

Citations 19

Authors

Li Xu

Wei-Lin Liao

Qi-Jue Lu

Peng Zhang

Ji Zhu

Ge-Ning Jiang

Affiliations

Soon will be listed here.

Abstract

Hypoxia is a common feature of solid tumors and has been associated with tumor aggressiveness and poor prognosis. Exosomes are involved in mediating cellular-environment interactions. Circular RNAs (circRNAs) are a class of non-coding RNA broadly found in cells and exosomes. However, the functions and regulatory mechanisms of exosomal circRNAs induced by hypoxia remain poorly understood in lung adenocarcinoma (LUAD) development. Differentially expressed circRNAs were identified between exosomes extracted from hypoxic and normoxic conditions through microarray analysis. We focused on hsa-circ-0003439 found on chromosome 1 and derived from SET domain bifurcated histone lysine methyltransferase 1 (SETDB1), and thus we named it circSETDB1. We discovered that exosomes obtained from hypoxic LUAD cells improved the migration, invasion, and proliferation capacity of normoxic LUAD cells. circSETDB1 was found to be significantly upregulated in hypoxia-induced exosomes from LUAD cell lines compared with exosomes in the normal condition. Moreover, knockdown of significantly inhibited cell malignant growth . Importantly, we showed that circSETDB1 was upregulated in serum exosomes in LUAD patients, and exosomal circSETDB1 levels were closely associated with disease stage. Finally, using RNA immunoprecipitation (RIP), bioinformatics, and luciferase reporter assays, we elucidated the implication of a circSETDB1/miR-7/specificity protein 1 (Sp1) axis in the development and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma.

Citing Articles

Circular RNAs in human diseases.

Wang Y, Zhang J, Yang Y, Liu Z, Sun S, Li R MedComm (2020). 2024; 5(9):e699.

PMID: 39239069 PMC: 11374765. DOI: 10.1002/mco2.699.

SP1 undergoes phase separation and activates RGS20 expression through super-enhancers to promote lung adenocarcinoma progression.

Shan L, Wang W, Du L, Li D, Wang Y, Xie Y Proc Natl Acad Sci U S A. 2024; 121(29):e2401834121.

PMID: 38976739 PMC: 11260144. DOI: 10.1073/pnas.2401834121.

Exosomal circRNA: emerging insights into cancer progression and clinical application potential.

Zhang F, Jiang J, Qian H, Yan Y, Xu W J Hematol Oncol. 2023; 16(1):67.

PMID: 37365670 PMC: 10294326. DOI: 10.1186/s13045-023-01452-2.

Circular RNA circFBXO7 attenuates non-small cell lung cancer tumorigenesis by sponging miR-296-3p to facilitate KLF15-mediated transcriptional activation of CDKN1A.

Wang Z, Ye L, Xiang X, Wei X, Niu Y, Peng W Transl Oncol. 2023; 30:101635.

PMID: 36774884 PMC: 9945757. DOI: 10.1016/j.tranon.2023.101635.

Exosomal circular RNA: a signature for lung cancer progression.

Hussen B, Abdullah S, Faraj G, Rasul M, Salihi A, Ghafouri-Fard S Cancer Cell Int. 2022; 22(1):378.

PMID: 36457039 PMC: 9714134. DOI: 10.1186/s12935-022-02793-7.

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