Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis
Abstract Background Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. Methods Differentially expressed circRNAs in GC and h...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-08-01
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| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-02976-w |
| _version_ | 1797752646105300992 |
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| author | Xiao-juan Huang Yan Wang Hui-ting Wang Zhao-feng Liang Cheng Ji Xiao-xi Li Lei-lei Zhang Run-bi Ji Wen-rong Xu Jian-hua Jin Hui Qian |
| author_facet | Xiao-juan Huang Yan Wang Hui-ting Wang Zhao-feng Liang Cheng Ji Xiao-xi Li Lei-lei Zhang Run-bi Ji Wen-rong Xu Jian-hua Jin Hui Qian |
| author_sort | Xiao-juan Huang |
| collection | DOAJ |
| description | Abstract Background Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. Methods Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. Results Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a “ceRNA” for miR-4659a/b-3p to increase HBEGF and TGF-β/Smad expression, then promoted the development of GC. Conclusions Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-β/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC. |
| first_indexed | 2024-03-12T17:06:29Z |
| format | Article |
| id | doaj.art-cdac207328d24bd0ad2443be18528175 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-12T17:06:29Z |
| publishDate | 2023-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-cdac207328d24bd0ad2443be185281752023-08-06T11:25:20ZengBMCCancer Cell International1475-28672023-08-0123111510.1186/s12935-023-02976-wExosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axisXiao-juan Huang0Yan Wang1Hui-ting Wang2Zhao-feng Liang3Cheng Ji4Xiao-xi Li5Lei-lei Zhang6Run-bi Ji7Wen-rong Xu8Jian-hua Jin9Hui Qian10Wujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityWujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu UniversityWujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityThe Laboratory Department, The Affiliated People’s Hospital of Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityWujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu UniversityWujin Institute of Molecular Diagnostics and Precision Cancer Medicine of Jiangsu University, Wujin Hospital Affiliated with Jiangsu UniversityAbstract Background Exosome, a component of liquid biopsy, loaded protein, DNA, RNA and lipid gradually emerges as biomarker in tumors. However, exosomal circRNAs as biomarker and function mechanism in gastric cancer (GC) are not well understood. Methods Differentially expressed circRNAs in GC and healthy people were screened by database. The identification of hsa_circ_000200 was verified by RNase R and sequencing, and the expression of hsa_circ_000200 was evaluated using qRT-PCR. The biological function of hsa_circ_000200 in GC was verified in vitro. Western blot, RIP, RNA fluorescence in situ hybridization, and double luciferase assay were utilized to explore the potential mechanism of hsa_circ_000200. Results Hsa_circ_000200 up-regulated in GC tissue, serum and serum exosomes. Hsa_circ_000200 in serum exosomes showed better diagnostic ability than that of tissues and serum. Combined with clinicopathological parameters, its level was related to invasion depth, TNM staging, and distal metastasis. Functionally, knockdown of hsa_circ_000200 inhibited GC cells proliferation, migration and invasion in vitro, while its overexpression played the opposite role. Importantly, exosomes with up-regulated hsa_circ_000200 promoted the proliferation and migration of co-cultured GC cells. Mechanistically, hsa_circ_000200 acted as a “ceRNA” for miR-4659a/b-3p to increase HBEGF and TGF-β/Smad expression, then promoted the development of GC. Conclusions Our findings suggest that hsa_circ_000200 promotes the progression of GC through hsa_circ_000200/miR-4659a/b-3p/HBEGF axis and affecting the expression of TGF-β/Smad. Serum exosomal hsa_circ_000200 may serve as a potential biomarker for GC.https://doi.org/10.1186/s12935-023-02976-wExosomeshsa_circ_000200Gastric cancerLiquid biopsy markermiR-4659a/b-3pHBEGF |
| spellingShingle | Xiao-juan Huang Yan Wang Hui-ting Wang Zhao-feng Liang Cheng Ji Xiao-xi Li Lei-lei Zhang Run-bi Ji Wen-rong Xu Jian-hua Jin Hui Qian Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis Cancer Cell International Exosomes hsa_circ_000200 Gastric cancer Liquid biopsy marker miR-4659a/b-3p HBEGF |
| title | Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis |
| title_full | Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis |
| title_fullStr | Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis |
| title_full_unstemmed | Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis |
| title_short | Exosomal hsa_circ_000200 as a potential biomarker and metastasis enhancer of gastric cancer via miR-4659a/b-3p/HBEGF axis |
| title_sort | exosomal hsa circ 000200 as a potential biomarker and metastasis enhancer of gastric cancer via mir 4659a b 3p hbegf axis |
| topic | Exosomes hsa_circ_000200 Gastric cancer Liquid biopsy marker miR-4659a/b-3p HBEGF |
| url | https://doi.org/10.1186/s12935-023-02976-w |
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