SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner
Tao Li,1,* Yingchun Wan,2,* Ziyuan Su,3 Jiayu Li,4 Minna Han,5 Changyu Zhou6 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 2Department of Endocrinology, China-Japan Union Hospital of Jilin University, Cha...
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| Format: | Article |
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Dove Medical Press
2020-07-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/srf-potentiates-colon-cancer-metastasis-and-progression-in-a-microrna--peer-reviewed-article-CMAR |
| _version_ | 1818968253518577664 |
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| author | Li T Wan Y Su Z Li J Han M Zhou C |
| author_facet | Li T Wan Y Su Z Li J Han M Zhou C |
| author_sort | Li T |
| collection | DOAJ |
| description | Tao Li,1,* Yingchun Wan,2,* Ziyuan Su,3 Jiayu Li,4 Minna Han,5 Changyu Zhou6 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 2Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 3Department of Pharmacy, Changchun Second Hospital, Changchun 130062, Jilin, People’s Republic of China; 4Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 5Department of Medicine, Medical School of Chinese People & Apos’s Liberation Army, Chinese People & Apos’s Liberation Army General Hospital, Beijing 100853, People’s Republic of China; 6Department of Digestion, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyu ZhouDepartment of Digestion, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of ChinaTel/ Fax +86-431-84995850Email drZhouCY1224@163.comObjective: Serum response factor (SRF), a sequence-specific transcription factor, is closely related to metastasis of gastric cancer, a digestive tract cancer. Herein, we probed the effect of SRF on metastasis and progression of colon cancer (CC), another digestive tract disorder, and the detailed mechanism.Methods: Microarray analysis was conducted on tumor and adjacent tissues to filter differentially expressed miRNA, followed by RT-qPCR validation in CC cell lines. The transcription factor and the target gene of microRNA-214 (miR-214) were predicted, and their binding relationships were tested by luciferase reporter assays and ChIP assays. Subsequently, SRF and protein tyrosine kinase 6 (PTK6) expression in CC patients and cells was evaluated by RT-qPCR, while JAK2 and STAT3 expression in cells by Western blot analysis. To further explore functions of miR-214, PTK6 and SRF on CC, CC cells were delivered with si-PTK6, miR-214 mimic and/or SRF overexpression.Results: miR-214 expressed poorly in CC tissues and cell lines, which related to advanced TNM staging and survival. miR-214 mimic inhibited proliferation, migration, invasion, xenograft tumor growth and metastasis of CC cells. SRF, overexpressed in CC samples and cells, suppressed the transcription of miR-214. Meanwhile, SRF upregulation counteracted the inhibitory role of miR-214 mimic in CC cell growth. miR-214 negatively regulated PTK6 expression to impair the JAK2/STAT3 pathway activation, thereby halting CC cell proliferation, migration, invasion, xenograft tumor growth and metastasis.Conclusion: Altogether, miR-214 may perform as a tumor suppressor in CC, and the SRF/miR-214/PTK6/JAK2/STAT3 axis could be applied as a biomarker and potential therapeutic target.Keywords: SRF, microRNA-214, PTK6, Colon cancer, The JAK2/STAT3 pathway |
| first_indexed | 2024-12-20T14:01:45Z |
| format | Article |
| id | doaj.art-b3b66fb470ee40c08062b66d1d9fe65b |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-20T14:01:45Z |
| publishDate | 2020-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-b3b66fb470ee40c08062b66d1d9fe65b2022-12-21T19:38:21ZengDove Medical PressCancer Management and Research1179-13222020-07-01Volume 126477649155714SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent MannerLi TWan YSu ZLi JHan MZhou CTao Li,1,* Yingchun Wan,2,* Ziyuan Su,3 Jiayu Li,4 Minna Han,5 Changyu Zhou6 1Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 2Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 3Department of Pharmacy, Changchun Second Hospital, Changchun 130062, Jilin, People’s Republic of China; 4Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China; 5Department of Medicine, Medical School of Chinese People & Apos’s Liberation Army, Chinese People & Apos’s Liberation Army General Hospital, Beijing 100853, People’s Republic of China; 6Department of Digestion, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changyu ZhouDepartment of Digestion, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People’s Republic of ChinaTel/ Fax +86-431-84995850Email drZhouCY1224@163.comObjective: Serum response factor (SRF), a sequence-specific transcription factor, is closely related to metastasis of gastric cancer, a digestive tract cancer. Herein, we probed the effect of SRF on metastasis and progression of colon cancer (CC), another digestive tract disorder, and the detailed mechanism.Methods: Microarray analysis was conducted on tumor and adjacent tissues to filter differentially expressed miRNA, followed by RT-qPCR validation in CC cell lines. The transcription factor and the target gene of microRNA-214 (miR-214) were predicted, and their binding relationships were tested by luciferase reporter assays and ChIP assays. Subsequently, SRF and protein tyrosine kinase 6 (PTK6) expression in CC patients and cells was evaluated by RT-qPCR, while JAK2 and STAT3 expression in cells by Western blot analysis. To further explore functions of miR-214, PTK6 and SRF on CC, CC cells were delivered with si-PTK6, miR-214 mimic and/or SRF overexpression.Results: miR-214 expressed poorly in CC tissues and cell lines, which related to advanced TNM staging and survival. miR-214 mimic inhibited proliferation, migration, invasion, xenograft tumor growth and metastasis of CC cells. SRF, overexpressed in CC samples and cells, suppressed the transcription of miR-214. Meanwhile, SRF upregulation counteracted the inhibitory role of miR-214 mimic in CC cell growth. miR-214 negatively regulated PTK6 expression to impair the JAK2/STAT3 pathway activation, thereby halting CC cell proliferation, migration, invasion, xenograft tumor growth and metastasis.Conclusion: Altogether, miR-214 may perform as a tumor suppressor in CC, and the SRF/miR-214/PTK6/JAK2/STAT3 axis could be applied as a biomarker and potential therapeutic target.Keywords: SRF, microRNA-214, PTK6, Colon cancer, The JAK2/STAT3 pathwayhttps://www.dovepress.com/srf-potentiates-colon-cancer-metastasis-and-progression-in-a-microrna--peer-reviewed-article-CMARsrfmicrorna-214ptk6colon cancerthe jak2/stat3 pathway |
| spellingShingle | Li T Wan Y Su Z Li J Han M Zhou C SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner Cancer Management and Research srf microrna-214 ptk6 colon cancer the jak2/stat3 pathway |
| title | SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner |
| title_full | SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner |
| title_fullStr | SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner |
| title_full_unstemmed | SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner |
| title_short | SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner |
| title_sort | srf potentiates colon cancer metastasis and progression in a microrna 214 ptk6 dependent manner |
| topic | srf microrna-214 ptk6 colon cancer the jak2/stat3 pathway |
| url | https://www.dovepress.com/srf-potentiates-colon-cancer-metastasis-and-progression-in-a-microrna--peer-reviewed-article-CMAR |
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