Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells
Authors: Yu Chen
Xiuling Li
Wei Wang
Zhaoshen Li
Ling Lan
Suofeng Sun
Bowei Liu
Shuangyin Han
Journal: OncoTargets and therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: 5-fluorouracil; PTEN; apoptosis; miR-486-5p; pancreatic cancer.
Affiliations: Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, People's Republic of China., Department of Gastroenterology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, Henan 450003, People's Republic of China., Department of Gastroenterology, Nanhai Hospital, Southern Medical University, Foshan, Guangdong 528200, People's Republic of China.

Abstract:  Background: 5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Methods: Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay. Results: In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model. Conclusion: We found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer. 

Retracted: No

PubPeer comments:
 The authors appear to have accidentally uploaded the same images twice (lime boxes in the image below). They should probably contact the journal for a correction. ![file] , 
 Dear friends! Thanks very much for your kind attention and pointing out the mistakes in our article. We have noticed the Figure 1 should be changed, since weu00a0accidentally uploaded the same images twice in Figure 1E due to carelessness. And we have contacted the editorial office of the journal (OncoTargets and Therapy )and ask them to help us to publish a corrigendum. The corrected Fig 1 was attached below. We sincerely apologized for this unintentional error made during manuscript submission. We stand by the quality of the experiments and the conclusions in the paper. And we have received a reply from the editorial office, and the corrected data will be published very soon.![file] ,