Cancer Management and Research (Jul 2020)
SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner
Abstract
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 [email protected]: 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
