Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression

Abstract Background Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gas...

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Main Authors: Jing Zhang, Hui Liu, Lidan Hou, Ge Wang, Rui Zhang, Yanxia Huang, Xiaoyu Chen, Jinshui Zhu
Format: Article
Language:English
Published: BMC 2017-09-01
Series:Molecular Cancer
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12943-017-0719-3
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author Jing Zhang
Hui Liu
Lidan Hou
Ge Wang
Rui Zhang
Yanxia Huang
Xiaoyu Chen
Jinshui Zhu
author_facet Jing Zhang
Hui Liu
Lidan Hou
Ge Wang
Rui Zhang
Yanxia Huang
Xiaoyu Chen
Jinshui Zhu
author_sort Jing Zhang
collection DOAJ
description Abstract Background Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined. Methods The correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion. Results Increased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. Conclusion circLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC.
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spelling doaj.art-2f07cb53fce341cdb1d2f21d80bc2b9c2022-12-21T20:19:10ZengBMCMolecular Cancer1476-45982017-09-0116111610.1186/s12943-017-0719-3Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expressionJing Zhang0Hui Liu1Lidan Hou2Ge Wang3Rui Zhang4Yanxia Huang5Xiaoyu Chen6Jinshui Zhu7Department of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalDepartment of Gastroenterology, Shanghai Jiao Tong University Affiliated Sixth People’s HospitalAbstract Background Non-coding RNAs (ncRNAs) have been shown to regulate gene expression involved in tumor progression of multiple malignancies. Our previous studies indicated that large tumor suppressor kinase 1 (LATS1), a core part of Hippo signaling pathway, functions as a tumor suppressor in gastric cancer (GC). But, the underlying molecular mechanisms by which ncRNAs modulate LATS1 expression in GC remain undetermined. Methods The correlation of LATS1 and has-miR-424-5p (miR-424) expression with clinicopathological characteristics and prognosis of GC patients was analyzed by TCGA RNA-sequencing data. A novel circular RNA_LARP4 (circLARP4) was identified to sponge miR-424 by circRNA expression profile and bioinformatic analysis. The binding site between miR-424 and LATS1 or circLARP4 was verified using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The expression and localization of circLARP4 in GC tissues were investigated by fluorescence in situ hybridization (FISH). MTT, colony formation, Transwell and EdU assays were performed to assess the effects of miR-424 or circLARP4 on cell proliferation and invasion. Results Increased miR-424 expression or decreased LATS1 expression was associated with pathological stage and unfavorable prognosis of GC patients. Ectopic expression of miR-424 promoted proliferation and invasion of GC cells by targeting LATS1 gene. Furthermore, circLARP4 was mainly localized in the cytoplasm and inhibited biological behaviors of GC cells by sponging miR-424. The expression of circLARP4 was downregulated in GC tissues and represented an independent prognostic factor for overall survival of GC patients. Conclusion circLARP4 may act as a novel tumor suppressive factor and a potential biomarker in GC.http://link.springer.com/article/10.1186/s12943-017-0719-3Circular RNA_LARP4miR-424-5pLATS1InvasionGastric cancer
spellingShingle Jing Zhang
Hui Liu
Lidan Hou
Ge Wang
Rui Zhang
Yanxia Huang
Xiaoyu Chen
Jinshui Zhu
Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
Molecular Cancer
Circular RNA_LARP4
miR-424-5p
LATS1
Invasion
Gastric cancer
title Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
title_full Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
title_fullStr Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
title_full_unstemmed Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
title_short Circular RNA_LARP4 inhibits cell proliferation and invasion of gastric cancer by sponging miR-424-5p and regulating LATS1 expression
title_sort circular rna larp4 inhibits cell proliferation and invasion of gastric cancer by sponging mir 424 5p and regulating lats1 expression
topic Circular RNA_LARP4
miR-424-5p
LATS1
Invasion
Gastric cancer
url http://link.springer.com/article/10.1186/s12943-017-0719-3
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