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Circular RNA circNHSL1 Contributes to Gastric Cancer Progression Through the miR-149-5p/YWHAZ Axis

Authors Hui C, Tian L, He X

Received 9 March 2020

Accepted for publication 27 June 2020

Published 12 August 2020 Volume 2020:12 Pages 7117—7130

DOI https://doi.org/10.2147/CMAR.S253152

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Ahmet Emre Eskazan


Chunying Hui,1 Lei Tian,1 Xinling He2

1The Third Digestive Ward, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, People’s Republic of China; 2Department of Hand and Foot Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning 121000, People’s Republic of China

Correspondence: Xinling He
Department of Hand and Foot Surgery, The First Affiliated Hospital of Jinzhou Medical University, No. 2, Section 5, Renmin Street, Jinzhou, Liaoning 121000, People’s Republic of China
Tel +86-416-4197260
Email ticlbd@163.com

Background: Gastric cancer (GC) is a considerable health burden around the world. Circular RNA Nance-Horan syndrome-like 1 (circNHSL1) is reported to be highly expressed in GC. Nevertheless, the function and molecule mechanism of circNHSL1 are still unclear.
Methods: The expression levels of circNHSL1, microRNA-149-5p (miR-149-5p) and YWHAZ were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The subcellular fractionation identified the remarkable cytoplasmic localization of circNHSL1. Cell migration and invasion were measured by transwell assays. The levels of glutamine, glutamate and α-ketoglutarate (α-KG) were assessed by the corresponding kit. The protein levels of CD63, CD9, CD81, alanine, serine, cysteine-preferring transporter 2 (ASCT2), glutaminase 1 (GLS1), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) were detected by Western blot assay. The binding relationship between miR-149-5p and circNHSL1 or YWHAZ was predicted by starBase 3.0 and then verified by RNA pull-down and dual-luciferase reporter assays. Xenograft tumor model examined the biological role of circNHSL1 in vivo. Exosomes were examined by a transmission electron microscope and nanoparticle tracking analysis (NTA).
Results: CircNHSL1 was highly expressed in GC cell-derived exosomes, GC tissues, and cells. Its knockdown impeded GC cell migration, invasion, and glutaminolysis. Mechanism analysis showed that circNHSL1 could affect YWHAZ expression by sponging miR-149-5p, thereby regulating GC progression. CircNHSL1 downregulation blocked GC tumor growth in vivo.
Conclusion: Our studies disclosed that circNHSL1 knockdown repressed migration, invasion, and glutaminolysis in vitro and inhibited tumor growth in vivo by miR-149-5p/YWHAZ axis in GC, implying an underlying circRNA-targeted therapy for GC treatment.

Keywords: circNHSL1, miR-149-5p, YWHAZ, gastric cancer

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