CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling
Abstract Background Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). Materi...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-020-00697-0 |
| _version_ | 1818725646011990016 |
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| author | Fang Wang Xiaochun Wang Jingruo Li Pengwei Lv Mingli Han Lin Li Zhuo Chen Lingling Dong Nan Wang Yuanting Gu |
| author_facet | Fang Wang Xiaochun Wang Jingruo Li Pengwei Lv Mingli Han Lin Li Zhuo Chen Lingling Dong Nan Wang Yuanting Gu |
| author_sort | Fang Wang |
| collection | DOAJ |
| description | Abstract Background Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). Materials and methods qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. Results CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. Conclusions CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients. |
| first_indexed | 2024-12-17T21:45:37Z |
| format | Article |
| id | doaj.art-51a7ca969c644f398ae6eac6b598d74c |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-17T21:45:37Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-51a7ca969c644f398ae6eac6b598d74c2022-12-21T21:31:28ZengBMCJournal of Biomedical Science1423-01272021-01-0128111610.1186/s12929-020-00697-0CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signalingFang Wang0Xiaochun Wang1Jingruo Li2Pengwei Lv3Mingli Han4Lin Li5Zhuo Chen6Lingling Dong7Nan Wang8Yuanting Gu9Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, Affiliated Hospital of Hebei UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityAbstract Background Circular RNAs (circRNAs) have caught increasing attentions and interests for their important involvement in cancer initiation and progression. This study aims to investigate the biological functions of circNOL10 and its potential molecular mechanisms in breast cancer (BC). Materials and methods qRT-PCR and western blot assays were performed to measure the expression of related genes. CCK-8, colony formation, flow cytomerty and transwell assays were used to assess cell proliferation, cell cycle, migration and invasion. RNA pull-down, luciferase reporter and RIP assays were applied to address the potential regulatory mechanism of circNOL10. Results CircNOL10 was down-regulated in BC tissues and cells. Low expression of circNOL10 was associated with larger tumor size, advanced TNM stage, lymph node metastasis and unfavorable prognosis. Overexpression of circNOL10 inhibited cell proliferation, migration, invasion and EMT in vitro and slowed xenograft tumor growth in vivo. Mechanistically, circNOL10 could act as a molecular sponge for miR-767-5p, leading to the up-regulation of suppressors of cytokine signaling 2 (SOCS2) and inactivation of JAK2/STAT5 pathway. Moreover, circNOL10-mediated suppression of malignant phenotypes was attenuated by miR-767-5p. Similar to circNOL10, enforced expression of SOCS2 also resulted in the suppression of cell proliferation and metastasis. Furthermore, knockdown of SOCS2 reversed the tumor-suppressive effect induced by circNOL10. Conclusions CircNOL10 repressed BC development via inactivation of JAK2/STAT5 signaling by regulating miR-767-5p/SOCS2 axis. Our findings offer the possibility of exploiting circNOL10 as a therapeutic and prognostic target for BC patients.https://doi.org/10.1186/s12929-020-00697-0Breast cancerCircular RNAcircNOL10miR-767-5pSOCS2JAK/STAT signaling |
| spellingShingle | Fang Wang Xiaochun Wang Jingruo Li Pengwei Lv Mingli Han Lin Li Zhuo Chen Lingling Dong Nan Wang Yuanting Gu CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling Journal of Biomedical Science Breast cancer Circular RNA circNOL10 miR-767-5p SOCS2 JAK/STAT signaling |
| title | CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling |
| title_full | CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling |
| title_fullStr | CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling |
| title_full_unstemmed | CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling |
| title_short | CircNOL10 suppresses breast cancer progression by sponging miR-767-5p to regulate SOCS2/JAK/STAT signaling |
| title_sort | circnol10 suppresses breast cancer progression by sponging mir 767 5p to regulate socs2 jak stat signaling |
| topic | Breast cancer Circular RNA circNOL10 miR-767-5p SOCS2 JAK/STAT signaling |
| url | https://doi.org/10.1186/s12929-020-00697-0 |
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