<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

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 tumorsuppressive 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.

TPX2 Enhanced the Activation of the HGF/ETS-1 Pathway and Increased the Invasion of Endocrine-Independent Prostate Carcinoma Cells

“…In these processes, the destruction of the local extracellular matrix by tumor cells and the destruction of the extracellular matrix at the site of metastasis during metastasis are the key steps for its proliferation, metastasis, and invasion (33)(34)(35). This step is mediated by ETS -1; and the activated ETS-1 can destroy the extracellular matrix and normal tissue structure by mediating its downstream genes (the various matrix metalloproteinases) (36)(37)(38). In the present work, the invasion of PC-3 cells was examined using the in vitro (transwell) or in vivo model (the nude mice model).…”

Robust Validation and Comprehensive Analysis of a Novel Signature Derived from Crucial Metabolic Pathways of Pancreatic Ductal Adenocarcinoma

“…TPI1, also named ETS proto-oncogene 1 (ETS1), works as a downstream transcription factor of HIF-1a, which increases in a hypoxic environment and is highly correlated with recurrence rate of intrahepatic cholangiocarcinoma patients [ 75 , 76 ]. TPI1 is modulated by miR-381, miR-769-5p and prostaglandin E2, which demonstrates its key role in PDAC [ 77 , 78 , 79 ]. Cytidine deaminase (CDA) is another independent factor in the present study.…”

Systematic evaluation, verification and comparison of tuberculosis‐related non‐coding RNA diagnostic panels

“…Linear combination used in Cui 2017 took into account both the miRNA expression of each dataset itself and the weight of included variables, which might confer its excellent generalization ability. However, a miRNA extensively participates in various biological and physiological pathways and thus has potential to be a biomarker for several different diseases, such as miR769_5p, miR320a and miR22_3p in Cui 2017 41‐43 . Multiple roles of miRNAs in biological activities can decrease their specificity in a given disease.…”

“…Cui 2017 [41][42][43]. Multiple roles of miRNAs in biological activities can The performance of 13 miRNA models in all available miRNA datasets…”