Anti-cancer effect of Aquaporin 5 silencing in colorectal cancer cells in association with inhibition of Wnt/β-catenin pathway

Wang, Wei; Li, Qing; Yang, Tao; Li, Dongsheng; Ding, Feng; Sun, Hongzhi; Bai, Guang

doi:10.1007/s10616-017-0147-7

Cited by 22 publications

(18 citation statements)

References 41 publications

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“…44 Inhibition of PAR2 suppresses EMT and promotes the chemo-resistance of CRC to 5-FU. 45 Previous study showed that AQP5 silencing has an anti-cancer effect via regulating Wnt/β-catenin pathway and EMT progress, 46,47 which is consistent with our research. Additionally, AQP5 promotes hepatocellular carcinoma metastasis via modulating NF-κB-regulated EMT progress.…”

Section: Discussionsupporting

confidence: 90%

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

Zhou

Kong

et al. 2020

Cancer Biology & Therapy

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Background: Studies showed that microRNAs (miRNAs) are important regulators in drug resistance. The current study investigated the role of miR-185-3p and its predicted target gene AQP5 in 5-FU-insensitive colorectal cancer (CRC) cells. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) and Spearman's correlation analysis were conducted to determine the correlation of expression levels of miR-185-3p and AQP5 from CRC tissues. HCT-116 and HCT-8 cells were treated by gradient concentration of 5-FU to construct 5-FU-resistant CRC model. The inhibition and viability of 5-FU-resistant cells were detected by MTT assay, and cell migration and invasion ability were determined by wound healing and transwell assay. The expressions of miR-185-3p and AQP5 were measured by qRT-PCR. StarBase and dual-luciferase reporter assay were used to predict and confirm the interaction between miR-185-3p and AQP5. Further experiments were performed to explore the function of miR-185-3p in 5-FU-resistant cells through regulating aquaporin-5 (AQP5). The levels of EMT-associated markers and AQP5 were determined by conducting Western Blot and qRT-PCR. Results: We found that 5-FU-resistant CRC cells showed a lower inhibition rate, and higher migration and invasion abilities. MiR-185-3p was low-expressed in CRC tissues and 5-FU-resistance cells, and it targeted and regulated the expression of AQP5, which was found up-regulated in CRC and 5-FU-resistance CRC cells (r = −0.29, P < .05). Furthermore, miR-185-3p mimic enhanced the chemo-sensitivity of 5-FU-resistant cells, while overexpressed AQP5 reversed such an effect produced by miR-185-3p mimic. Conclusion: MiR-185-3p mimic enhances the chemosensitivity of CRC cells via AQP5. Our research provides a potential therapeutic target for 5-FU-resistant CRC cells.

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Section: Discussionsupporting

confidence: 90%

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

Zhou

Kong

et al. 2020

Cancer Biology & Therapy

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“…It was shown that AQP3 was also involved in prostate cancer cell motility and invasion through ERK1/2-mediated matrix metallopeptidase 3 secretion (56). Epithelial cells undergoing EMT gain motility and invasiveness, which are characteristic features of metastatic cells (57), and AQP5 knockdown in various cancer cells indicated that AQP5 overexpression promotes EMT (9,58). However, our data indicate that AQP5 regulation of adhesion proteins in MDCK cells, a noncancerous cell line, is independent of EMT (10).…”

Section: Discussionmentioning

confidence: 69%

Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

Jensen

Pedersen

et al. 2019

FASEB j.

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Plasticity of epithelial cell‐cell adhesion is vital in epithelial homeostasis and is regulated in multiple processes associated with cell migration, such as embryogenesis and wound healing. In cancer, cell‐cell adhesion is compromised and is associated with increased cell migration and metastasis. Aquaporin (AQP) water channels facilitate water transport across cell membranes and are essential in the regulation of body water homeostasis. Increased expression of several AQPs, especially AQP5, is associated with increased cancer cell migration, metastasis, and poor prognosis. We found that AQP5 overexpression in normal epithelial cells induced cell detachment and dissemination from migrating cell sheets. AQP5 reduced both cell‐cell coordination during collective migration and overall distance covered by the migrating cell sheets. AQP5 and the isoforms AQP1 and AQP4 decreased, whereas AQP3 increased, levels of plasma membrane‐associated lateral junctional proteins. This regulation was mediated by the cytoplasmic domains of the AQPs. This shows that the AQPs have dual functions in epithelial physiology: as channel proteins and as differential regulators of cell‐cell adhesiveness. This regulation may contribute to dynamic regulation of cell junctions in processes such as embryogenesis and wound healing and also explain the pivotal roles of AQPs in carcinogenesis and metastasis.—Login, F. H., Jensen, H. H., Pedersen, G. A., Koffman, J. S., Kwon, T.‐H., Parsons, M., Nejsum, L. N. Aquaporins differentially regulate cell‐cell adhesion in MDCK cells. FASEB J. 33, 6980–6994 (2019). http://www.fasebj.org

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“…5e). β-catenin is a key factor that activates upstream and downstream factors of the Wnt/β-catenin signaling pathway (19). The mrna and protein expression levels of β-catenin were also significantly decreased in MCF-7 and Mda-MB-231 cells treated with 400 and 800 µg/ml aPS compared with the control group ( Fig.…”

Section: Aps Inhibits Breast Cancer Cell Invasion Invasion Is Anmentioning

confidence: 87%

“…The present results demonstrated that aPS reduced the expression levels of cytoplasmic and nuclear β-catenin in a dose-dependent manner. additionally, cyclin d1 and c-Myc are produced following β-catenin activation (19). c-Myc, a nuclear protein transcription factor, is associated with the activation of genes that are related to multiple cellular processes, such as proliferation, differentiation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…among these inducers, the Wnt/β-catenin signaling pathway, which can be divided into classical and non-classical signaling pathways, has attracted increasing attention (17). Wnt has been identified as the promoter of the pathway (18) and, as an upstream factor, β-catenin affects the expression of downstream factors of the signaling pathway, including c-Myc and cyclin d1 (19). Previous studies have suggested that the Wnt/β-catenin signaling pathway can influence developmental embryonic processes, determine cell polarity and regulate cell proliferation (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

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Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

Yang

Sun

et al. 2020

Mol Med Report

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epithelial-mesenchymal transition (eMT) serves an important role in tumor migration and invasion. Astragalus polysaccharide (aPS), which is the main component of the traditional chinese medicine Astragalus membranaceus, has been identified to display an antitumor effect. However, the effects and mechanisms of aPS during breast cancer migration and invasion are not completely understood. The present study investigated whether aPS inhibited breast cancer migration and invasion by modulating the eMT pathway. an MTT assay and a Ki67 immunofluorescence staining assay demonstrated that aPS inhibited the proliferation of breast cancer cells. The results of the wound healing and Transwell Matrigel invasion assays suggested that aPS decreased the migration and invasion of breast cancer cells. The western blotting and immunofluorescence analyses further demonstrated that aPS had a regulatory effect on eMT-related molecules. aPS decreased the expression levels of Snail and vimentin, but increased e-cadherin expression. aPS also downregulated Wnt1, β-catenin and downstream target expression. additionally, the present results suggested that aPS decreased the proliferation, and eMT-mediated migration and invasion of cells by inhibiting the Wnt/β-catenin signaling pathway. The present study suggested that aPS may serve as a promising therapeutic agent for breast cancer.

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Anti-cancer effect of Aquaporin 5 silencing in colorectal cancer cells in association with inhibition of Wnt/β-catenin pathway

Cited by 22 publications

References 41 publications

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

MiR-185-3p mimic promotes the chemosensitivity of CRC cells via AQP5

Aquaporins differentially regulate cell‐cell adhesion in MDCK cells

Astragalus polysaccharide inhibits breast cancer cell migration and invasion by regulating epithelial‑mesenchymal transition via the Wnt/β‑catenin signaling pathway

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