Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis
Autor: | Ze-Guo Chen, Nianfeng Li, Jian-Hua Wang, Hui Luo, Ling Liu, Li Jiarong |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
Endocrinology
Diabetes and Metabolism Cell Cycle Proteins 0302 clinical medicine Endocrinology Cell Movement Gene knockdown Chemistry miR-448 MMP ‐ matrix metallopeptidase Cell migration LncRNA DUXAP8 PC ‐ pancreatic carcinoma Long non-coding RNA Cell biology WTAP ATCC ‐ American Type Culture Collection Blot Gene Expression Regulation Neoplastic PBS ‐ phosphate-buffered saline 030220 oncology & carcinogenesis 030211 gastroenterology & hepatology RNA Long Noncoding RNA Splicing Factors ceRNA ‐ competing endogenous RNAs Signal Transduction miRNAs ‐ microRNAs lncRNAs ‐ long noncoding RNAs Fak ‐ focal adhesion kinase Cell Line Focal adhesion 03 medical and health sciences Downregulation and upregulation Cell Line Tumor Sequence Homology Nucleic Acid microRNA Internal Medicine Humans Neoplasm Invasiveness Cell Proliferation Hepatology pancreatic carcinoma Fak Base Sequence Cell growth Original Articles qPCR ‐ quantitative polymerase chain reaction Pancreatic Neoplasms MicroRNAs HEK293 Cells Focal Adhesion Kinase 1 WTAP ‐ Wilms tumor 1–associating protein |
Zdroj: | Pancreas |
ISSN: | 1536-4828 0885-3177 |
Popis: | Objectives Pancreatic carcinoma (PC) has become the fourth leading cause of cancer deaths. Long noncoding RNA DUXAP8 has also been reported to play a regulatory role in PC progression. However, its molecular mechanism in PC is not fully elucidated. Methods Quantitative real-time polymerase chain reaction was used to detect the levels of DUXAP8, microRNA (miR)-448, Wilms tumor 1-associating protein (WTAP), focal adhesion kinase (Fak), and matrix metallopeptidase 2/9. Western blotting was carried out to detect matrix metallopeptidase 2/9, WTAP, Fak, and p-Fak. The interaction between DUXAP8 and miR-448 as well as WTAP and miR-448 was validated by bioinformatics and dual-luciferase reporter assays. Transwell assay was used to analyze cell invasion and migration. 3-[4,5-Dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay was used to analyze cell proliferation. Results DUXAP8 was upregulated, whereas miR-448 was downregulated in PC tissue and cells. Meanwhile, DUXAP8 knockdown or miR-448 overexpression inhibited migration, invasion, and proliferation of PC cells. DUXAP8 directly targeted miR-448, and miR-448 directly bound to WTAP. Downregulation of miR-448 reversed the inhibition of migration and invasion of PC cells by DUXAP8 knockdown. Conclusions DUXAP8 sponges miR-448 to modulate migration, invasion, and proliferation of PC cells, indicating a novel mechanistic role of DUXAP8 in the regulation of PC progression. |
Databáze: | OpenAIRE |
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