Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway

Abstract Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overe...

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Main Authors: Yixun Lu, Guoxiao Liu, Yanjun Wang, Kai Li, Xinxin Xu, Benlong Zhang, Lin Chen, Hongqing Xi, Xinxin Wang
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:MedComm – Oncology
Subjects:
Online Access:https://doi.org/10.1002/mog2.39
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author Yixun Lu
Guoxiao Liu
Yanjun Wang
Kai Li
Xinxin Xu
Benlong Zhang
Lin Chen
Hongqing Xi
Xinxin Wang
author_facet Yixun Lu
Guoxiao Liu
Yanjun Wang
Kai Li
Xinxin Xu
Benlong Zhang
Lin Chen
Hongqing Xi
Xinxin Wang
author_sort Yixun Lu
collection DOAJ
description Abstract Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR‐665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit‐8, 5‐Ethynyl‐2′‐deoxyuridine, clone formation assay, Transwell invasion assay, wound‐healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR‐665 sponges and facilitate GC growth and metastasis via modulating miR‐665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3‐kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR‐665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.
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spelling doaj.art-572b791ecd324a41bf7e276718184e5a2023-10-09T10:56:48ZengWileyMedComm – Oncology2769-64482023-06-0122n/an/a10.1002/mog2.39Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathwayYixun Lu0Guoxiao Liu1Yanjun Wang2Kai Li3Xinxin Xu4Benlong Zhang5Lin Chen6Hongqing Xi7Xinxin Wang8Department of Anesthesiology The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of Health Medicine The Second Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaDepartment of General Surgery The First Medical Center of Chinese PLA General Hospital Beijing ChinaAbstract Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide. Compelling evidence indicates that circular RNA (circRNA) played critical roles in multiple cancers. However, the role and mechanisms of circRNAs in GC remains unclear. Here we first identified a notably overexpressed circular RNA hsa_circ_0025506 in GC by human circRNA microarray, designated as circGPRC5A(e2). Next, we found circGPRC5A(e2) was overexpressed in GC cell lines and clinical samples as well. Then, we confirmed that circGPRC5A(e2) was primarily located in the cytoplasm of GC cells and colocation phenomenon was observed with miR‐665 via fluorescence in situ hybridization. Functionally, Cell Counting Kit‐8, 5‐Ethynyl‐2′‐deoxyuridine, clone formation assay, Transwell invasion assay, wound‐healing assay, and animal experiments showed that circGPRC5A(e2) promoted GC proliferation, migration, and invasion in vitro, and tumorigenesis and metastasis in vivo. Mechanistically, we showed that circGPRC5A(e2) could serve as miR‐665 sponges and facilitate GC growth and metastasis via modulating miR‐665/LIM and SH3 protein 1 (LASP1) axis and activating phosphatidylinositol 3‐kinase/AKT pathway. Taken together, this study revealed that circGPRC5A(e2) functioned as an oncogene in GC. The circGPRC5A(e2)/miR‐665/LASP1 axis revealed by current research might provide novel biomarkers and promising therapeutic targets for GC.https://doi.org/10.1002/mog2.39circGPRC5A(e2)gastric cancerLIM and SH3 protein 1miR‐665
spellingShingle Yixun Lu
Guoxiao Liu
Yanjun Wang
Kai Li
Xinxin Xu
Benlong Zhang
Lin Chen
Hongqing Xi
Xinxin Wang
Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
MedComm – Oncology
circGPRC5A(e2)
gastric cancer
LIM and SH3 protein 1
miR‐665
title Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
title_full Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
title_fullStr Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
title_full_unstemmed Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
title_short Circular RNA circGPRC5A(e2) facilitates gastric cancer progression and metastasis via modulating miR‐665/LASP1 and activating PI3K/AKT pathway
title_sort circular rna circgprc5a e2 facilitates gastric cancer progression and metastasis via modulating mir 665 lasp1 and activating pi3k akt pathway
topic circGPRC5A(e2)
gastric cancer
LIM and SH3 protein 1
miR‐665
url https://doi.org/10.1002/mog2.39
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