Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis

被引:17
作者
Li, Jia-Rong [1 ]
Liu, Ling [1 ]
Luo, Hui [1 ]
Chen, Ze-Guo [1 ]
Wang, Jian-Hua [1 ]
Li, Nian-Feng [1 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Biliopancreat Surg, 87 Xiangya Rd, Changsha 410008, Hunan, Peoples R China
关键词
pancreatic carcinoma; LncRNA DUXAP8; miR-448; WTAP; Fak; PC - pancreatic carcinoma; lncRNAs - long noncoding RNAs; ceRNA - competing endogenous RNAs; WTAP - Wilms tumor 1-associating protein; Fak - focal adhesion kinase; miRNAs; -; microRNAs; ATCC - American Type Culture Collection; PBS - phosphate-buffered saline; qPCR - quantitative polymerase chain reaction; MMP - matrix metallopeptidase; EPITHELIAL-MESENCHYMAL TRANSITION; COMPETING ENDOGENOUS RNA; CANCER CELLS; PROLIFERATION; EXPRESSION; GROWTH; LNCRNA; EPIDEMIOLOGY;
D O I
10.1097/MPA.0000000000001751
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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.
引用
收藏
页码:317 / 326
页数:10
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