Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway
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 treatme...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-01-01
|
| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13046-020-01791-9 |
| _version_ | 1828931385931333632 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Jiacheng Cao |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T00:46:12Z |
| format | Article |
| id | doaj.art-f0f514c6f5bd4bcb951203422580b34b |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-14T00:46:12Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-f0f514c6f5bd4bcb951203422580b34b2022-12-21T23:24:06ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-01-0140111710.1186/s13046-020-01791-9Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathwayJiacheng Cao0Xing Zhang1Penghui Xu2Haixiao Wang3Sen Wang4Lu Zhang5Zheng Li6Li Xie7Guangli Sun8Yiwen Xia9Jialun Lv10Jing Yang11Zekuan Xu12Department of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of General Surgery, The First Affiliated Hospital of Nanjing Medical UniversityAbstract 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.https://doi.org/10.1186/s13046-020-01791-9Gastric cancercircRNAmiRNAWNT2GlutaminolysisHNRNPL |
| spellingShingle | 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 Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway Journal of Experimental & Clinical Cancer Research Gastric cancer circRNA miRNA WNT2 Glutaminolysis HNRNPL |
| title | Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway |
| title_full | Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway |
| title_fullStr | Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway |
| title_full_unstemmed | Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway |
| title_short | Circular RNA circLMO7 acts as a microRNA-30a-3p sponge to promote gastric cancer progression via the WNT2/β-catenin pathway |
| title_sort | circular rna circlmo7 acts as a microrna 30a 3p sponge to promote gastric cancer progression via the wnt2 β catenin pathway |
| topic | Gastric cancer circRNA miRNA WNT2 Glutaminolysis HNRNPL |
| url | https://doi.org/10.1186/s13046-020-01791-9 |
| work_keys_str_mv | AT jiachengcao circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT xingzhang circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT penghuixu circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT haixiaowang circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT senwang circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT luzhang circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT zhengli circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT lixie circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT guanglisun circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT yiwenxia circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT jialunlv circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT jingyang circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway AT zekuanxu circularrnacirclmo7actsasamicrorna30a3pspongetopromotegastriccancerprogressionviathewnt2bcateninpathway |