&lt;p&gt;Numb inhibits cell proliferation, invasion, and epithelial&amp;ndash;mesenchymal transition through PAK1/&amp;beta;-catenin signaling pathway in ovarian cancer&lt;/p&gt;

Liang, Jinqian; Han, Bingbing; Zhang, Yunhe; Yue, Qingfen

doi:10.2147/ott.s194725

Cited by 13 publications

(14 citation statements)

References 44 publications

(40 reference statements)

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“…NUMB is an endocytic adaptor protein that is localized in the basement layer of polarized epithelial cells (14). In previous studies, NUMB has been found to serve crucial roles in human cancer (15)(16)(17)(18); for example, NUMB expression levels were decreased in ovarian cancer, which regulated cancer cell proliferation, invasion and epithelial-mesenchymal transition through regulating the p21 (RAC1) activated kinase 1/β-catenin signaling pathway (15). NUMB expression levels were also decreased in tongue cancer and its overexpression inhibited cell proliferation, migration and invasion via regulating Notch1 signaling (16).…”

Section: Discussionmentioning

confidence: 99%

microRNA‑146b promotes neuroblastoma cell growth through targeting NUMB

Zhang

et al. 2020

Exp Ther Med

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Accumulating evidence has demonstrated that the abnormal expression of microRNA (miRNA/miR) serves a crucial role in the development of numerous types of human cancer, including neuroblastoma (NB). The present study aimed to investigate the expression levels and biological roles of miR-146b in NB. miR-146b expression levels in NB cell lines and human umbilical vein endothelial cells (HUVECs) were analyzed using reverse transcription-quantitative PCR, and the regulatory effects of miR-146b on NB cell proliferation, invasion and apoptosis in vitro were investigated using CCK-8 assay, transwell invasion assay and flow cytometry. In addition, bioinformatics analysis, western blotting and dual-luciferase reporter assays were used to determine whether NUMB was a target gene of miR-146b. miR-146b expression levels were increased in NB cell lines compared with HUVECs. The knockdown of miR-146b using a miR-146b inhibitor significantly inhibited NB cell proliferation and invasion, but promoted cell apoptosis in vitro. Furthermore, it was revealed that miR-146b promoted NB cell proliferation through targeting NUMB. In conclusion, miR-146b was suggested to serve as an oncogene, at least in part, through directly targeting NUMB, which indicated that miR-146b may be a potential therapeutic target for NB treatment.

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Section: Discussionmentioning

confidence: 99%

microRNA‑146b promotes neuroblastoma cell growth through targeting NUMB

Zhang

et al. 2020

Exp Ther Med

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“…Additionally, PAKs have been involved in certain pathological conditions, including cancer [14]. Upregulation of PAK1 was reported in diverse human cancers, such like thyroid cancer [15], ovarian cancer [16], bladder cancer [17] and TSCC [18]. Through bioinformatic analysis, we observed that PAK1 could bind with miR-26a/miR-26b.…”

Section: Introductionmentioning

confidence: 91%

MiR-26a/miR-26b represses tongue squamous cell carcinoma progression by targeting PAK1

et al. 2020

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Background: Tongue squamous cell carcinoma (TSCC) is the most common oral malignancy. Previous studies found that microRNA (miR)-26a and miR-26b were downregulated in TSCC tissues. The current study was designed to explore the effects of miR-26a/miR-26b on TSCC progression and the potential mechanism. Methods: Expression of miR-26a, miR-26b and p21 Activated Kinase 1 (PAK1) in TSCC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Flow cytometry analysis was performed to examine cell cycle and apoptosis. Transwell assay was conducted to evaluate the migrated and invasive abilities of SCC4 and Cal27 cells. In addition, western blot assay was employed to analyze the protein level. Glucose assay kit and lactate assay kit were utilized to analyze glycolysis. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were applied to explore the relationship between miR-26a/miR-26b and PAK1. Xenograft tumor model was constructed to explore the role of miR-26a/miR-26b in vivo. Results: Both miR-26a and miR-26b were underexpressed, while PAK1 was highly enriched in TSCC. Overexpression of miR-26a and miR-26b inhibited TSCC cell cycle, migration invasion and glycolysis, while promoted cell apoptosis. Both miR-26a and miR-26b directly targeted and negatively regulated PAK1 expression. Introduction of PAK1 partially reversed miR-26a/miR-26b upregulation-mediated cellular behaviors in TSCC cells. Gain of miR-26a/miR-26b blocked TSCC tumor growth in vivo. Conclusion: MiR-26a/miR-26b repressed TSCC progression via targeting PAK1 in vitro and in vivo, which enriched our understanding about TSCC development and provided new insights into the its treatment.

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“…It displayed complex and multiple functions including the control of asymmetric cell division and cell fate choice, endocytosis, cell adhesion and migration, ubiquitination of specific substrates, and a variety of signaling pathways (Notch, Hedgehog, MDM2-p53, and WNT signaling) [ 8 – 10 ]. Accumulated evidence showed that Numb acts as a tumor-suppressive role in medulloblastoma [ 10 ], breast cancer [ 11 ], non-small cell lung cancer (NSCLC) [ 12 ], ovarian cancer [ 13 ], and colorectal cancer [ 14 ]. On the other hand, overexpression of Numb was found in hepatocellular carcinoma [ 15 ], astrocytomas [ 16 ], and cervical squamous carcinoma cells [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Numb-PRRL promotes TGF-β1- and EGF-induced epithelial-to-mesenchymal transition in pancreatic cancer

et al. 2022

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Isoform-specific functions of Numb in the development of cancers, especially in the initiation of epithelial-to-mesenchymal transition (EMT) remains controversial. We study the specific function of Numb-PRRL isoform in activated EMT of pancreatic ductal adenocarcinoma (PC), which is distinguished from our previous studies that only focused on the total Numb protein. Numb-PRRL isoform was specifically overexpressed and silenced in PC cells combining with TGF-β1 and EGF stimulus. We systematically explored the potential effect of Numb-PRRL in the activated EMT of PC in vitro and in vivo. The total Numb protein was overexpressed in the normal pancreatic duct and well-differentiated PC by IHC. However, Numb-PRRS isoform but not Numb-PRRL showed dominant expression in PC tissues. Numb-PRRL overexpression promoted TGF-β1-induced EMT in PANC-1 and Miapaca-2 cells. TGF-β1-induced EMT-like cell morphology, cell invasion, and migration were enhanced in Numb-PRRL overexpressing groups following the increase of N-cadherin, Vimentin, Smad2/3, Snail1, Snail2, and cleaved-Notch1 and the decrease of E-cadherin. Numb-PRRL overexpression activated TGFβ1-Smad2/3-Snail1 signaling was significantly reversed by the Notch1 inhibitor RO4929097. Conversely, Numb-PRRL silencing inhibited EGF-induced EMT in AsPC-1 and BxPC-3 cells following the activation of EGFR-ERK/MAPK signaling via phosphorylating EGFR at tyrosine 1045. In vivo, Numb-PRRL overexpression or silencing promoted or inhibited subcutaneous tumor size and distant liver metastases via regulating EMT and Snail signaling, respectively. Numb-PRRL promotes TGF-β1- and EGF-induced EMT in PC by regulating TGF-β1-Smad2/3-Snail and EGF-induced EGFR-ERK/MAPK signaling.

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<p>Numb inhibits cell proliferation, invasion, and epithelial–mesenchymal transition through PAK1/β-catenin signaling pathway in ovarian cancer</p>

Cited by 13 publications

References 44 publications

microRNA‑146b promotes neuroblastoma cell growth through targeting NUMB

microRNA‑146b promotes neuroblastoma cell growth through targeting NUMB

MiR-26a/miR-26b represses tongue squamous cell carcinoma progression by targeting PAK1

Numb-PRRL promotes TGF-β1- and EGF-induced epithelial-to-mesenchymal transition in pancreatic cancer

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