<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>
Authors: Lan Feng
Kai Cheng
Changhong Yu
Shuang Yu
Nannan Chi
Journal: OncoTargets and Therapy (2020)
Discipline: CLINICAL MEDICINE
Keywords: ETS proto-oncogene 1; invasion; microRNA-769-5p; pancreatic ductal adenocarcinoma; proliferation.
Affiliations: Department of Gastroenterology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China., Department of Infectious Diseases, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China., Department of Cardiovascular Medicine, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang 154002, People's Republic of China.

Abstract:  Purpose: MicroRNA-769-5p (miR-769) is aberrantly expressed and plays crucial roles in non-small cell lung cancer and melanoma. However, the expression pattern, biological role, and mechanisms of action of miR-769 in pancreatic ductal adenocarcinoma (PDAC) are yet to be fully elucidated. Therefore, we attempted to determine the potential regulatory function of miR-769 in PDAC progression and to explore the underlying mechanisms in detail. Methods: In this study, reverse-transcription quantitative polymerase chain reaction was carried out to determine the expression profile of miR-769 in PDAC. A series of experiments, including a Cell Counting Kit-8 assay, flow-cytometric analysis, Transwell migration and invasion assays, and a xenograft animal model, were applied to test whether miR-769 affects the malignancy of PDAC. Results: We found that miR-769 was significantly underexpressed in PDAC tissues and cell lines. The low miR-769 expression significantly correlated with the TNM stage and lymph node metastasis. Patients with PDAC harboring low miR-769 expression showed shorter overall survival than did the patients with high miR-769 expression. Forced upregulation of miR-769 suppressed PDAC cell proliferation, migration, and invasion in vitro; promoted apoptosis in vitro; and hindered tumor growth in vivo. Experiments on the mechanism identified ETS proto-oncogene 1 (ETS1) as a direct target gene of miR-769 in PDAC cells. Furthermore, ETS1 turned out to be upregulated in PDAC tissue samples, and the upregulation of ETS1 negatively correlated with miR-769 expression. Moreover, ETS1 knockdown simulated the tumor-suppressive effects of miR-769 overexpression on PDAC cells. Besides, ETS1 reintroduction attenuated the antitumor actions of miR-769 upregulation in PDAC cells. Conclusion: Our findings indicate that miR-769 performs tumor-suppressive functions in PDAC by directly targeting ETS1, and this miRNA may represent a potential therapeutic target for the development of anticancer therapies. 

Retracted: Yes

PubPeer comments:
 https: twitter.com houndcl status 1263144560122671105 Can you double check the sgmRNA copy numbers, especially the BAL specimens? Some data are inconsitent between Fig. 4 and 5. 1. The peak sgmRNA copy number in Fig. 4B didn t exceed 6 copies ml, but Fig. 5 did have some points with 6 copies ml. 2. There are some monkeys have completely negative sgmRNA when challenged with live SARS-CoV-2. I collected the **n0 values (number of monkeys showing complete flat sgmRNA curve)** from Fig. 4B for each condition. However, total number of n0 monkeys doesn t match that in Fig. 4D and Fig. 5. ![file] ,