Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis
Abstract Background Circular RNAs (circRNAs) are a special kind of non-coding RNAs that are implicated in cancer malignant behavior, including glycolysis. However, their contributions to gastric cancer (GC) cell glycolysis are still poorly understood. In the present study, we aimed to investigate th...
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| Format: | Article |
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BMC
2020-05-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01256-1 |
| _version_ | 1828492630123610112 |
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| author | Jia Liu Haiying Liu Qingshan Zeng Pei Xu Mingxing Liu Ning Yang |
| author_facet | Jia Liu Haiying Liu Qingshan Zeng Pei Xu Mingxing Liu Ning Yang |
| author_sort | Jia Liu |
| collection | DOAJ |
| description | Abstract Background Circular RNAs (circRNAs) are a special kind of non-coding RNAs that are implicated in cancer malignant behavior, including glycolysis. However, their contributions to gastric cancer (GC) cell glycolysis are still poorly understood. In the present study, we aimed to investigate the glycolysis-related role of circ-MAT2B in GC. Methods Gene expression was determined by qRT-PCR analysis. Protein level was detected by Western blot. The CCK-8, colony and EdU assays were carried out to assess GC cell viability, colony formation and DNA synthesis rate. Glycolysis was determined by glucose uptake and lactate production. The positive regulatory network of circ-MAT2B/miR-515-5p/HIF-1α was identified by RNA pull-down, RIP, ChIP and luciferase reporter assays. The in vivo role of circ-MAT2B was evaluated by using xenograft tumor model. Results Circ-MAT2B was notably increased in GC and could be used as a sensitive and specific indicator of GC diagnosis and prognosis. Stable knockdown of circ-MAT2B dramatically inhibited GC cell viability, colony formation, DNA synthesis, glucose uptake and lactate production in vitro, and retarded tumor growth in vivo. Mechanistically, circ-MAT2B was dominantly located in the cytoplasm and acted as a ceRNA to sponge miR-515-5p and increase HIF-1α expression. Silencing of miR-515-5p or overexpression of HIF-1α could evidently rescue the attenuated aggressive phenotype of GC cells caused by circ-MAT2B knockdown. Importantly, HIF-1α was able to directly bind to circ-MAT2B promoter and transcriptionally activate circ-MAT2B, thus forming a positive feedback loop. Conclusion Our data suggest that circ-MAT2B is a oncogenic circRNA in GC and provide a promising therapeutic target for GC patients. |
| first_indexed | 2024-12-11T11:24:01Z |
| format | Article |
| id | doaj.art-15292969cb8d4d1dbddcb3dce14dc855 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T11:24:01Z |
| publishDate | 2020-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-15292969cb8d4d1dbddcb3dce14dc8552022-12-22T01:09:03ZengBMCCancer Cell International1475-28672020-05-0120111210.1186/s12935-020-01256-1Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axisJia Liu0Haiying Liu1Qingshan Zeng2Pei Xu3Mingxing Liu4Ning Yang5Department of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityDepartment of Nutriology, The Third Affiliated Hospital of Guangzhou Medical UniversityAbstract Background Circular RNAs (circRNAs) are a special kind of non-coding RNAs that are implicated in cancer malignant behavior, including glycolysis. However, their contributions to gastric cancer (GC) cell glycolysis are still poorly understood. In the present study, we aimed to investigate the glycolysis-related role of circ-MAT2B in GC. Methods Gene expression was determined by qRT-PCR analysis. Protein level was detected by Western blot. The CCK-8, colony and EdU assays were carried out to assess GC cell viability, colony formation and DNA synthesis rate. Glycolysis was determined by glucose uptake and lactate production. The positive regulatory network of circ-MAT2B/miR-515-5p/HIF-1α was identified by RNA pull-down, RIP, ChIP and luciferase reporter assays. The in vivo role of circ-MAT2B was evaluated by using xenograft tumor model. Results Circ-MAT2B was notably increased in GC and could be used as a sensitive and specific indicator of GC diagnosis and prognosis. Stable knockdown of circ-MAT2B dramatically inhibited GC cell viability, colony formation, DNA synthesis, glucose uptake and lactate production in vitro, and retarded tumor growth in vivo. Mechanistically, circ-MAT2B was dominantly located in the cytoplasm and acted as a ceRNA to sponge miR-515-5p and increase HIF-1α expression. Silencing of miR-515-5p or overexpression of HIF-1α could evidently rescue the attenuated aggressive phenotype of GC cells caused by circ-MAT2B knockdown. Importantly, HIF-1α was able to directly bind to circ-MAT2B promoter and transcriptionally activate circ-MAT2B, thus forming a positive feedback loop. Conclusion Our data suggest that circ-MAT2B is a oncogenic circRNA in GC and provide a promising therapeutic target for GC patients.http://link.springer.com/article/10.1186/s12935-020-01256-1circ-MAT2BmiR-515-5pHIF-1αGlycolysis |
| spellingShingle | Jia Liu Haiying Liu Qingshan Zeng Pei Xu Mingxing Liu Ning Yang Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis Cancer Cell International circ-MAT2B miR-515-5p HIF-1α Glycolysis |
| title | Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis |
| title_full | Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis |
| title_fullStr | Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis |
| title_full_unstemmed | Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis |
| title_short | Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis |
| title_sort | circular rna circ mat2b facilitates glycolysis and growth of gastric cancer through regulating the mir 515 5p hif 1α axis |
| topic | circ-MAT2B miR-515-5p HIF-1α Glycolysis |
| url | http://link.springer.com/article/10.1186/s12935-020-01256-1 |
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