Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion

Abstract Background The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissue...

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Main Authors: Xin Xu, Shoulian Wang, Haibo Wang, Chunpeng Pan, Wenyan Yang, Jiwei Yu
Format: Article
Language:English
Published: BMC 2021-12-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-021-09052-4
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author Xin Xu
Shoulian Wang
Haibo Wang
Chunpeng Pan
Wenyan Yang
Jiwei Yu
author_facet Xin Xu
Shoulian Wang
Haibo Wang
Chunpeng Pan
Wenyan Yang
Jiwei Yu
author_sort Xin Xu
collection DOAJ
description Abstract Background The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissues, in regulating GC biological behaviour. Methods High-throughput RNA sequencing was used to identify differentially expressed genes between normal gastric tissues and GC tissues; actinomycin D and RNase R assays were used to determine the stability and loop structure of hsa_circ_0008434; and the miRanda database was used to predict the target genes of hsa_circ_0008434. The role of hsa_circ_0008434 in cell proliferation, migration, and invasion was examined using CCK-8, wound healing, Transwell and colony formation assays. The regulatory relationships among hsa_circ_0008434, microRNA-6838 (miR-6838), and ubiquitin-specific peptidase 9X (USP9X) were determined by dual-luciferase activity assays. The expression of hsa_circ_0008434 and miR-6838 was measured by qPCR; the expression of USP9X was detected by immunohistochemistry and Western blotting. The effects of hsa_circ_0008434 on in vivo tumour growth were assessed in xenograft models. Results We found that hsa_circ_0008434 was one of the most upregulated circRNAs in GC tissue versus normal tissue. Further in vitro testing indicated that by acting as a miRNA sponge for miR-6838-5p, hsa_circ_0008434 promotes the expression of USP9X and further increases the proliferation, migration, and invasion of GC cells. In addition, animal studies indicated that hsa_circ_0008434 could promote tumour growth in vivo. Conclusions Hsa_circ_0008434 may promote GC proliferation, invasion and migration by regulating the expression of miR-6838 and USP9X.
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spelling doaj.art-05bbe9c136c440b2a39bb2edadba86412022-12-21T23:11:54ZengBMCBMC Cancer1471-24072021-12-0121111210.1186/s12885-021-09052-4Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasionXin Xu0Shoulian Wang1Haibo Wang2Chunpeng Pan3Wenyan Yang4Jiwei Yu5Department of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityDepartment of General Surgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong UniversityAbstract Background The role of circular RNAs (circRNAs) in the occurrence and development of gastric cancer (GC) has recently attracted increasing interest. The following study investigates the role of a newly discovered hsa_circ_0008434, which has been confirmed to be highly expressed in GC tissues, in regulating GC biological behaviour. Methods High-throughput RNA sequencing was used to identify differentially expressed genes between normal gastric tissues and GC tissues; actinomycin D and RNase R assays were used to determine the stability and loop structure of hsa_circ_0008434; and the miRanda database was used to predict the target genes of hsa_circ_0008434. The role of hsa_circ_0008434 in cell proliferation, migration, and invasion was examined using CCK-8, wound healing, Transwell and colony formation assays. The regulatory relationships among hsa_circ_0008434, microRNA-6838 (miR-6838), and ubiquitin-specific peptidase 9X (USP9X) were determined by dual-luciferase activity assays. The expression of hsa_circ_0008434 and miR-6838 was measured by qPCR; the expression of USP9X was detected by immunohistochemistry and Western blotting. The effects of hsa_circ_0008434 on in vivo tumour growth were assessed in xenograft models. Results We found that hsa_circ_0008434 was one of the most upregulated circRNAs in GC tissue versus normal tissue. Further in vitro testing indicated that by acting as a miRNA sponge for miR-6838-5p, hsa_circ_0008434 promotes the expression of USP9X and further increases the proliferation, migration, and invasion of GC cells. In addition, animal studies indicated that hsa_circ_0008434 could promote tumour growth in vivo. Conclusions Hsa_circ_0008434 may promote GC proliferation, invasion and migration by regulating the expression of miR-6838 and USP9X.https://doi.org/10.1186/s12885-021-09052-4hsa_circ_0008434Gastric cancerProliferationMigrationInvasion
spellingShingle Xin Xu
Shoulian Wang
Haibo Wang
Chunpeng Pan
Wenyan Yang
Jiwei Yu
Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
BMC Cancer
hsa_circ_0008434
Gastric cancer
Proliferation
Migration
Invasion
title Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
title_full Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
title_fullStr Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
title_full_unstemmed Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
title_short Hsa_circ_0008434 regulates USP9X expression by sponging miR-6838-5p to promote gastric cancer growth, migration and invasion
title_sort hsa circ 0008434 regulates usp9x expression by sponging mir 6838 5p to promote gastric cancer growth migration and invasion
topic hsa_circ_0008434
Gastric cancer
Proliferation
Migration
Invasion
url https://doi.org/10.1186/s12885-021-09052-4
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