<p>SRF Potentiates Colon Cancer Metastasis and Progression in a microRNA-214/PTK6-Dependent Manner</p>
Authors: Jiayu Li
Changyu Zhou
Yingchun Wan
Minna Han
Tao Li
Ziyuan Su
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: Colon cancer; PTK6; SRF; The JAK2/STAT3 pathway; microRNA-214.
Affiliations: Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People's Republic of China., Department of Endocrinology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People's Republic of China., Department of Pharmacy, Changchun Second Hospital, Changchun 130062, Jilin, People's Republic of China., Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People's Republic of China., Department 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., Department of Digestion, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, People's Republic of China.

Abstract:  Objective: 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. 

Retracted: No

PubPeer comments:
 Fig 7,  The JAK2 and STAT3 protein expression and phosphorylation in LOVO (A) and SW620 (B) cells transfected with SRF-NC, SRF-OE, miR-214 control, miR-214 mimic, miR-214 mimic + SRF-NC, miR-214 mimic + SRF-OE, PTK6-NC or si-PTK6 ![file] Surprisingly similar Western Blots, stylised in the same manner, illustrate [a corpus of at least 170 papers] (with 53 retracted so far, and 12 Expressions of Concern). E.g. Figs 5F, 6A, 7C, 9G from [Dong et al (2020)] . ![] Figs 4b from [Cui Zhu (2020)] , 3B from [Wang Zhao (2020)] , and 3D from [Wang, Yang Liang] (2020): ![] Figures 4D, 5B, 6A, 7A, 8E from [Deng et al (2018)] - an early manifestation. ![] , 
 Retracted [23 September 2022] . ------------------- The Editor and Publisher of Cancer Management and Research wish to retract the published article. Concerns were raised regarding the alleged similarity in features of the western blots from Figure 8A and B with those from unrelated papers. The authors responded to our queries but were unable to provide a satisfactory explanation for the alleged similarities, nor were they able to provide original data that could adequately verify the findings. The Editor requested to retract the article and the authors do not agree with this decision. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,