Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis
Abstract Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefor...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-021-04446-5 |
| _version_ | 1818245597322280960 |
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| author | Bopei Li Yeyang Chen Liang Liang Ye Wang Weijia Huang Kun Zhao Siyu Liu Guofei Deng Junqiang Chen |
| author_facet | Bopei Li Yeyang Chen Liang Liang Ye Wang Weijia Huang Kun Zhao Siyu Liu Guofei Deng Junqiang Chen |
| author_sort | Bopei Li |
| collection | DOAJ |
| description | Abstract Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC. |
| first_indexed | 2024-12-12T14:35:27Z |
| format | Article |
| id | doaj.art-7e771a071b74483f8ad5ed6bc0bcf479 |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-12-12T14:35:27Z |
| publishDate | 2022-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-7e771a071b74483f8ad5ed6bc0bcf4792022-12-22T00:21:23ZengNature Publishing GroupCell Death and Disease2041-48892022-03-0113311210.1038/s41419-021-04446-5Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axisBopei Li0Yeyang Chen1Liang Liang2Ye Wang3Weijia Huang4Kun Zhao5Siyu Liu6Guofei Deng7Junqiang Chen8Departments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First People’s Hospital of YulinDepartment of General Surgery, The Second Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityDepartments of Gastrointestinal Surgery, The First Affiliated Hospital of Guangxi Medical UniversityAbstract Gastric cancer (GC) is a heterogeneous disease with poor prognosis. Tumor-derived extracellular vesicles (EVs) assume a role in intercellular communication by carrying various molecules, including proteins, RNA, and DNAs, which has been identified to exhibit oncogenic effect in GC. Therefore, this research aimed to figure out whether tumor-derived EVs transmit c-Myc to orchestrate the growth and metastasis of GC. KCNQ1OT1, microRNA (miR)-556-3p and CLIC1 expression of GC tissues was detected through RT-qPCR. EVs were isolated from GC cells, followed by RT-qPCR and Western blot analysis of c-Myc expression in EVs and GC cells. Next, GC cells were incubated with EVs or transfected with a series of mimic, inhibitor, or siRNAs to assess their effects on cell viability, migrative, invasive, and apoptotic potential. Relationship among c-Myc, KCNQ1OT1, miR-556-3p, and CLIC1 was evaluated by dual-luciferase reporter assay. PI3K/AKT pathway-related proteins were assessed through Western blot analysis. KCNQ1OT1 and CLIC1 were highly expressed but miR-556-3p in GC tissues. c-Myc was high-expressed in tumor-derived EVs and GC cells. Mechanistically, c-Myc could induce KCNQ1OT1 expression, and KCNQ1OT1 bound to miR-556-3p that negatively targeted CLIC1 to inactivate PI3K/AKT pathway. Tumor-derived EVs, EVs-c-Myc, KCNQ1OT1 or CLIC1 overexpression, or miR-556-3p inhibition promoted GC cell proliferative, invasive, and migrative capacities but repressed their apoptosis through activating PI3K/AKT pathway. Collectively, tumor-derived EVs carrying c-Myc activated KCNQ1OT1 to downregulate miR-556-3p, thus elevating CLIC1 expression to activate the PI3K/AKT pathway, which facilitated the growth and metastasis of GC.https://doi.org/10.1038/s41419-021-04446-5 |
| spellingShingle | Bopei Li Yeyang Chen Liang Liang Ye Wang Weijia Huang Kun Zhao Siyu Liu Guofei Deng Junqiang Chen Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis Cell Death and Disease |
| title | Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis |
| title_full | Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis |
| title_fullStr | Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis |
| title_full_unstemmed | Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis |
| title_short | Tumor-derived extracellular vesicles shuttle c-Myc to promote gastric cancer growth and metastasis via the KCNQ1OT1/miR-556-3p/CLIC1 axis |
| title_sort | tumor derived extracellular vesicles shuttle c myc to promote gastric cancer growth and metastasis via the kcnq1ot1 mir 556 3p clic1 axis |
| url | https://doi.org/10.1038/s41419-021-04446-5 |
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