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Journal of Experimental & Clinical Cancer Research

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01-12-2021 | Gastric Cancer | Research

Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway

Authors: Jiacheng Cao, Xing Zhang, Penghui Xu, Haixiao Wang, Sen Wang, Lu Zhang, Zheng Li, Li Xie, Guangli Sun, Yiwen Xia, Jialun Lv, Jing Yang, Zekuan Xu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Background

Gastric cancer (GC) is one of the most common malignant tumors worldwide. Currently, the overall survival rate of GC is still unsatisfactory despite progress in diagnosis and treatment. Therefore, studying the molecular mechanisms involved in GC is vital for diagnosis and treatment. CircRNAs, a type of noncoding RNA, have been proven to act as miRNA sponges that can widely regulate various cancers. By this mechanism, circRNA can regulate tumors at the genetic level by releasing miRNA from inhibiting its target genes. The WNT2/β-Catenin regulatory pathway is one of the canonical signaling pathways in tumors. It can not only promote the development of tumors but also provide energy for tumor growth through cell metabolism (such as glutamine metabolism).

Methods

Through RNA sequencing, we found that hsa_circ_0008259 (circLMO7) was highly expressed in GC tissues. After verifying the circular characteristics of circLMO7, we determined the downstream miRNA (miR-30a-3p) of circLMO7 by RNA pull-down and luciferase reporter assays. We verified the effect of circLMO7 and miR-30a-3p on GC cells through a series of functional experiments, including colony formation, 5-ethynyl-2′-deoxyuridine and Transwell assays. Through Western blot and immunofluorescence analyses, we found that WNT2 was the downstream target gene of miR-30a-3p and further confirmed that the circLMO7-miR-30a-3p-WNT2 axis could promote the development of GC. In addition, measurement of related metabolites confirmed that this axis could also provide energy for the growth of GC cells through glutamine metabolism. We found that circLMO7 could promote the growth and metastasis of GC in vivo by the establishment of nude mouse models. Finally, we also demonstrated that HNRNPL could bind to the flanking introns of the circLMO7 exons to promote circLMO7 cyclization.

Results

CircLMO7 acted as a miR-30a-3p sponge affecting the WNT2/β-Catenin pathway to promote the proliferation, migration and invasion of GC cells. Moreover, animal results also showed that circLMO7 could promote GC growth and metastasis in vivo. CircLMO7 could also affect the glutamine metabolism of GC cells through the WNT2/β-Catenin pathway to promote its malignant biological function. In addition, we proved that HNRNPL could promote the self-cyclization of circLMO7.

Conclusions

CircLMO7 promotes the development of GC by releasing the inhibitory effect of miR-30a-3p on its target gene WNT2.

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Title: Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway
Authors: Jiacheng Cao
Xing Zhang
Penghui Xu
Haixiao Wang
Sen Wang
Lu Zhang
Zheng Li
Li Xie
Guangli Sun
Yiwen Xia
Jialun Lv
Jing Yang
Zekuan Xu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Gastric Cancer
Gastric Cancer
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-020-01791-9

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