Circular RNA circSATB2 promotes progression of non-small cell lung cancer cells

Nan Zhang,Yangyang Jia,Yiguo Jiang,Jialu Zhu,Aruo Nan,Miaoyun Qiu,Xin Li,Hanyu Zhou,Lijian Chen,Xin Dai,Han Zhang

doi:10.1186/s12943-020-01221-6

Abstract

BackgroundLung cancer has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Therapies for lung cancer have relatively poor outcomes and further improvements are required. Circular RNAs have been reported to participate in the occurrence and progression of cancer. Information on the functions and mechanism of circRNAs in lung cancer is limited and needs more exploration.MethodsWe detected expression of genes and proteins by qPCR and western blot. Function of circSATB2 was investigated using RNA interference and overexpression assays. Location of circSATB2 was assessed by fluorescence in situ hybridization (FISH). Interaction of circSATB2, miR-326 and FSCN1 was confirmed by dual-luciferase reporter assay.ResultsData from the investigation showed that circSATB2 was highly expressed in NSCLC cells and tissues. circSATB2 positively regulated fascin homolog 1, actin-bundling protein 1 (FSCN1) expression via miR-326 in lung cancer cells. Furthermore, circSATB2 can be transferred by exosomes and promote the proliferation, migration and invasion of NSCLC cells, as well as induce abnormal proliferation in normal human bronchial epithelial cells. Also, circSATB2 was highly expressed in serumal exosomes from lung cancer patients with high sensitivity and specificity for clinical detection and was related to lung cancer metastasis.ConclusionscircSATB2 participated in the progression of NSCLC and was differentially expressed in lung cancer tissue and serumal exosomes. circSATB2 may be potential biomarker for the diagnosis of NSCLC.

Highlights

Lung cancer has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases
To determine if these differentially expressed exosomal Circular RNA (circRNA) were functional in lung cancer, we assessed their expression in normal human bronchial epithelial cells (BEAS-2B and 16HBE cells) and NLCSC cells (H1299, H226, MES-1, H460, H661 and A549 cells). circ0008928 was highly and stably expressed in H460, A549 and H1299 cells compared with
FSCN1 mRNA levels in the circSATB2-OE + miR-326 mimic group decreased compared with the circSATB2-OE + miR-326 mimic NC group; indicating that miR-326 overexpression could rescue the increased FSCN1 mRNA levels induced by labeled the circSATB2 fluorescence in situ hybridization (FISH) probe, DAPI stained cell nuclei. b Cytoplasmic and nuclear circSATB2 expression detected by qPCR

Summary

Introduction

Lung cancer has high morbidity and mortality worldwide with non-small cell lung cancer (NSCLC) accounting for 85% of the cases. Therapies for lung cancer have relatively poor outcomes and further improvements are required. Circular RNAs have been reported to participate in the occurrence and progression of cancer. Information on the functions and mechanism of circRNAs in lung cancer is limited and needs more exploration. Lung cancer has been the leading cause of cancerrelated deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 85% of lung cancer cases [2, 3]. Despite extensive research and progress, therapies for lung cancer remain inadequate and further improvements are needed [4]. Exosomes have been implicated in the occurrence and development of many diseases, including cancer [6,7,8].

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Discussion

Conclusion