MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells (Retracted article. See vol. 122, 2021)
MicroRNA-300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/-catenin signaling pathway by targeting CUL4B in pancreatic cancer cells (Retracted article. See vol. 122, 2021)
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MicroRNA-300通过Wnt/-catenin信号通路靶向CUL4B促进胰腺癌细胞凋亡并抑制增殖、迁移、侵袭和上皮间质转化
DOI：
10.1002/jcb.26270
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Peng, Cheng-Hong
中科院分区：
文献类型：
--
作者：
Zhang, Jia-Qiang;Chen, Shi;Peng, Cheng-Hong
本研究旨在验证上调靶向CUL 4 B的microRNA-300（miR-300）通过调节Wnt/β-catenin信号通路促进胰腺癌细胞凋亡并抑制其增殖、迁移、侵袭和上皮-间质转化（EMT）的假说。收集110例胰腺癌患者的胰腺癌组织和癌旁组织。采用qRT-PCR和Western blot检测miR-300、CUL 4 B、Wnt、β-catenin、E-cadherin、N-cadherin、Snail、GSK-3和CyclinD 1的表达。将CFPAC-1、Capan-1和PANC-1分为空白、阴性对照（NC）、miR-300模拟物、miR-300抑制剂、siRNA-CUL 4 B和miR-300抑制剂+siRNA-CUL 4 B组。CCK-8法和Transwell法检测细胞增殖、迁移、侵袭能力、细胞周期分布和凋亡率。胰腺癌组织中CUL 4 B表达增加，但miR-300表达减少。当miR-300低表达时，CUL 4 B被上调，这反过来激活Wnt/β-catenin通路以保护β-catenin表达，从而诱导EMT。当miR-300高表达时，CUL 4 B下调，这反过来抑制Wnt/β-catenin途径以防止EMT。CUL 4 B组细胞迁移和侵袭能力减弱，凋亡增加。miR-300抑制剂组表现出生长速率的明显增加，伴随着最大的肿瘤体积。在miR-300模拟物和siRNA-CUL 4 B组中观察到较小的肿瘤体积和较慢的生长速率。我们的研究表明，低表达的miR-300可能有助于高表达的CUL 4 B激活Wnt/-catenin信号通路，进一步刺激EMT，从而促进胰腺癌细胞的增殖和迁移，但抑制凋亡。
The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, -catenin, E-cadherin, N-cadherin, Snail, GSK-3, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors+siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/-catenin pathway to protect the -catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.