Retracted: MicroRNA‐300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial‐mesenchymal transition via the Wnt/β‐catenin signaling pathway by targeting CUL4B in pancreatic cancer cells

Abstract

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 epithelialmesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/β-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, β-catenin, E-cadherin, N-cadherin, Snail, GSK-3β, 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/β-catenin pathway to protect the β-catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/β-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/β-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells. K E Y W O R D SCUL4B, epithelial-mesenchymal transition, invasion, microRNA-300, migration, pancreatic cancer, Wnt/β-catenin signaling pathway

Interaction between the Wnt/β‐catenin signaling pathway and the EMMPRIN/MMP‐2, 9 route in periodontitis

“…IHC staining of human gingival sections revealed that Wnt3a, β‐catenin, EMMPRIN and MMP‐2, 9 immunoreactivity was more abundant in the inflamed gingival tissue samples compared with that of the healthy group. Moreover, expression locations of β‐catenin extended from the cell membrane, which mediates intercellular adhesion by coordinating with E‐cadherin, to the cytoplasm and nucleus participating in the Wnt/β‐catenin pathway . Similarly, findings of the in vitro study concurred with those of IHC, Pg .…”

CUL4B regulates autophagy via JNK signaling in diffuse large B-cell lymphoma

“…As we alluded to above, emerging evidence had identified that CUL4B was highly expressed in different human malignancies, including carcinoma of the cervix, esophagus, liver, gastric and pancreatic cancer, and had a positive correlation with tumor progression [3,8,12,13,31]. Furthermore, CUL4B overexpression was significantly correlated with tumor size, advanced tumor stage, vascular and lymphatic invasion, distant metastasis, and histological differentiation, and was positively correlated with undesirable outcomes [3,[32][33][34].…”

The 14q32.31DLK1-DIO3 MIR300 tumor suppressorpromotes leukemogenesis by inducing cancer stem cell quiescence and inhibiting NK cell anti-cancer immunity

“…Twist1 and CTNNB1). MIR300-induced downregulation of CCND1, Twist1 and CTNNB1 was also observed in several solid tumors; however, this was associated with growth arrest/apoptosis but, unclearly, also with the acquisition by tumor cells of a pluripotent stem cell phenotype 16,20,21,46 .…”

“…3b). Note that CTNNB1, CCND1/2 and Twist1 are validated MIR300 targets 20,21 . Furthermore, consistent with the notion that high levels of active PP2A are not detrimental in normal CD34 + quiescent stem and committed progenitors 2,28 , CpG-miR-300 did not alter levels of MIR300 targets in CD34 + UCB cells ( Fig.…”

“…Among the miRNAs predicted in silico to re-activate PP2A in LSCs, we focused on hsa-MIR300 (MIR300) because it was predicted to activate PP2A upon inhibiting multiple PIP components and PP2A-regulated factors essential for CSC maintenance, cancer development/progression and G1/S cell cycle transition. The human MIR300 (MIR300) is an intergenic miRNA that belongs to the 14q32.31 DLK1-DIO3 genomic-imprinted tumor suppressor miRNA cluster B 16,17 ; it was found involved in loss-of heterozygosity, inhibited in several tumor types with high mitotic index and during epithelial-to-mesenchymal transition (EMT), and associated with a CSC phenotype [18][19][20][21][22] .…”