Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis.
Long Noncoding RNA DUXAP8 Promotes Pancreatic Carcinoma Cell Migration and Invasion Via Pathway by miR-448/WTAP/Fak Signaling Axis.
复制标题
DUXAP 8通过miR-448/WTAP/Fak信号轴促进胰腺癌细胞迁移和侵袭
DOI：
10.1097/mpa.0000000000001751
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发表时间：
2021-03-01
期刊：
影响因子：
2.9
通讯作者：
Li NF
中科院分区：
文献类型：
--
作者：
Li JR;Liu L;Luo H;Chen ZG;Wang JH;Li NF
胰腺癌（PC）已成为癌症死亡的第四大原因。长链非编码RNA DUXAP 8也被报道在PC进展中起调节作用。然而，其在PC中的分子机制尚未完全阐明。采用实时定量聚合酶链反应检测DUXAP 8、microRNA（miR）-448、Wilms肿瘤1相关蛋白（WTAP）、黏着斑激酶（Fak）和基质金属肽酶2/9的水平。Western blotting检测基质金属肽酶2/9、WTAP、Fak和p-Fak。DUXAP 8和miR-448以及WTAP和miR-448之间的相互作用通过生物信息学和双荧光素酶报告基因测定来验证。Transwell法检测细胞侵袭和迁移能力。3-[4，5-二甲基噻唑-2-基]-2，5二苯基溴化四唑测定用于分析细胞增殖。在PC组织和细胞中，DUXAP 8上调，而miR-448下调。同时，DUXAP 8敲低或miR-448过表达抑制PC细胞的迁移、侵袭和增殖。DUXAP 8直接靶向miR-448，而miR-448直接结合WTAP。下调miR-448可逆转DUXAP 8敲低对PC细胞迁移和侵袭的抑制作用。DUXAP 8海绵miR-448调节PC细胞的迁移，侵袭和增殖，表明DUXAP 8在PC进展的调节中的新机制作用。
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. 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. 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. 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.