Simultaneous overexpression of miR-126 and miR-34a induces a superior antitumor efficacy in pancreatic adenocarcinoma
Authors: Chunying Liu
Shu-De Feng
Changqing Su
Ziming Mao
Bin Sun
Minggao Guo
Yu-Song Nie
Journal: OncoTargets and therapy (2017)
Discipline: CLINICAL MEDICINE
Keywords: miR-126; miR-34a; oncolytic adenovirus; pancreatic cancer; target therapy.
Affiliations: Department of General Surgery, Jiangsu Armed Police General Hospital, Yangzhou, Jiangsu, China., Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital, National Center of Liver Cancer, Second Military Medical University, Shanghai, China., Department of General Surgery, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract:  Background: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due to its high degree of malignancy, increasing incidence, high mortality, and unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on PAC, implicating a possible application of miRNA in tumor therapy. However, the therapeutic effect of a single miRNA on pancreatic cancer is limited. Methods: We simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoembryonic antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined the antitumor efficacy of the therapeutic system in in vitro and in vivo experiments. Results: In vitro cytological experiments found that the expression levels of miR-126 and miR-34a were specifically increased in the AdCEAp-miR126/34a-infected PAC cells, and the antitumor efficacy was enhanced in aspects of cancer cell viability, migration, invasion, and apoptosis, by synergistically combining the antitumor effects of overexpressed miR-126 and miR-34a and the oncolytic effect of viral replication specifically in PAC cells. The expression levels of miR-126 target genes (vascular endothelial growth factor-A and SOX2) and miR-34a target genes (cyclin D1, E2F1, and Bcl-2) were markedly decreased in the PAC cells after being infected with AdCEAp-miR126/34a. Notable suppression of the therapeutic system on tumor growth was also proven in established PAC xenograft tumor models in nude mice, which demonstrated that the combination of miR-126 and miR-34a exerts more effective antitumor outcomes than a single miRNA. Conclusion: The therapeutic system co-expressing miR-126 and miR-34a mediated by oncolytic adenovirus is a promising system for PAC target therapy. 

Retracted: Yes

PubPeer comments:
 Figure 2A shows 4 different cell lines, but the Panc-1 photo appear to look very similar to the BxPC3 photo, although the intensity appears to be different. Shown with red boxes.  , 
 2020 retraction. https: www.dovepress.com retraction-simultaneous-overexpression-of-mir-126-and-mir-34a-induces--peer-reviewed-article-OTT The Editor-in-Chief and Publisher of OncoTargets and Therapy wish to retract the published article. Concerns were raised to the Editor-in-Chief regarding the possibility of some image manipulation in the published article. The alleged manipulation relates to Figure 2A AdCEAp-EGFP Panc-1 and AdCEAp-EGFP BxPC3. It appears the same image had been used in both panels but with the fluorescence intensity altered. The authors were asked for an explanation but were unable to provide a satisfactory explanation for the duplicated images and could not clearly account for the altered fluorescence intensity. The Editor-in-Chief raised doubts about the validity of the results and determined that simply replacing the images in question not been adequately justified by the authors. The authors wish to apologise for the error. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u201cRetractedu201d. ,