Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

RHBDD1 Promotes the Growth and Stemness Characteristics of Gastric Cancer Cells by Activating Wnt/β-catenin Signaling Pathway

Author(s): Yingxue Yang, Yuan Yuan and Boning Xia*

Volume 19, Issue 7, 2024

Published on: 13 October, 2023

Page: [1021 - 1028] Pages: 8

DOI: 10.2174/011574888X259932231010112521

Price: $65

Abstract

Backgrounds: Gastric cancer (GC) is threatening public health, with at least one million new cases reported each year. Rhomboid domain-containing protein 1 (RHBDD1) has been identified to regulate the proliferation, migration, and metastasis of cancer cells. However, the role of RHBDD1 in GC has not been elucidated.

Objects: This study aimed to investigate the role of RHBDD1 on the growth, metastasis, and stemness characteristics of GC.

Methods: RHBDD1 expression was analyzed from the TCGA databank. qRT-PCR was conducted to evaluate the transcription level of RHBDD1. Western blots were used to evaluate the protein expression of RHBDD1, CD133, CD44, Nanog, β-catenin and c-myc. Colony formation assay and transwell assay were conducted to evaluate the growth and metastasis of NCI-N87 cells, respectively. Sphere-forming assay was performed to study the stemness characteristics. The nude mice xenotransplantation model and immunohistochemistry (IHC) were performed to evaluate the growth of GC in vivo.

Results: RHBDD1 expression is elevated in GC cells and clinical tissues. RHBDD1 expression is positively associated with cell proliferation and metastasis of GC cells. RHBDD1 knockdown suppresses the expression of CD133, CD44 and Nanog and attenuates sphere-forming ability. RHBDD1 activates the Wnt/β-catenin pathway via promoting the expression of β-catenin / c-myc and inducing β-catenin translocation into nuclear. RHBDD1 knockdown inhibits the growth of GC in nude mice xenotransplantation model.

Conclusion: RHBDD1 is highly expressed in GC, and its knockdown inhibits the growth, metastasis and stemness characteristics of GC cells through activating the Wnt/β-catenin pathway, suggesting that RHBDD1 has the potential to be a novel therapeutic target for GC treatment.

« Previous Next »
Graphical Abstract

[1]
Zhu Z, Yu Z, Rong Z, et al. The novel GINS4 axis promotes gastric cancer growth and progression by activating Rac1 and CDC42. Theranostics 2019; 9(26): 8294-311.
[http://dx.doi.org/10.7150/thno.36256] [PMID: 31754397]
[2]
Huang T, Song X, Xu D, et al. Stem cell programs in cancer initiation, progression, and therapy resistance. Theranostics 2020; 10(19): 8721-43.
[http://dx.doi.org/10.7150/thno.41648] [PMID: 32754274]
[3]
Fu L, Bu L, Yasuda T, et al. Gastric cancer stem cells: Current insights into the immune microenvironment and therapeutic targets. Biomedicines 2020; 8(1): 7.
[http://dx.doi.org/10.3390/biomedicines8010007] [PMID: 31935894]
[4]
Chen L, Yang QC, Li YC, et al. Targeting CMTM6 Suppresses Stem Cell–Like Properties and Enhances Antitumor Immunity in Head and Neck Squamous Cell Carcinoma. Cancer Immunol Res 2020; 8(2): 179-91.
[http://dx.doi.org/10.1158/2326-6066.CIR-19-0394] [PMID: 31771985]
[5]
Xu J, Qin N, Jiang W, Chen T. Amygdalin suppresses the proliferation, migration and EMT of gastric cancer cells by inhibiting TGF-β/Smad signal pathway. Trop J Pharm Res 2022; 21(4): 721-6.
[http://dx.doi.org/10.4314/tjpr.v21i4.6]
[6]
Xu S, Zhang H, Wang A, Ma Y, Gan Y, Li G. Silibinin suppresses epithelial–mesenchymal transition in human non-small cell lung cancer cells by restraining RHBDD1. Cell Mol Biol Lett 2020; 25(1): 36.
[http://dx.doi.org/10.1186/s11658-020-00229-6] [PMID: 32528541]
[7]
Zhao C, Ling X, Li X, Hou X, Zhao D. MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1. Breast Cancer 2019; 26(6): 817-25.
[http://dx.doi.org/10.1007/s12282-019-00989-w] [PMID: 31243644]
[8]
Xu Z, Wang R, Li X, et al. RHBDD1 silencing inhibited cell growth and invasion of non-small cell lung cancer by mediating ZEB1/PI3K/AKT signaling pathway. J Mol Histol 2021; 52(3): 503-10.
[http://dx.doi.org/10.1007/s10735-020-09943-z] [PMID: 33515112]
[9]
Li M, Cai L, Wang X, et al. RHBDD1 promotes proliferation, migration, invasion and EMT in renal cell carcinoma via the EGFR/AKT signaling pathway. Mol Med Rep 2021; 24(6): 826.
[http://dx.doi.org/10.3892/mmr.2021.12466] [PMID: 34581421]
[10]
Zhang M, Miao F, Huang R, et al. RHBDD1 promotes colorectal cancer metastasis through the Wnt signaling pathway and its downstream target ZEB1. J Exp Clin Cancer Res 2018; 37(1): 1-14.
[http://dx.doi.org/10.1186/1756-9966-31-1] [PMID: 29301578]
[11]
Wang T, Zhang X, Liu W, Sun C, Li Z, Zhao D. Prognostic and Immunological Significance of Rhomboid Domain Containing Protein 1 in Multiple Primary Cancers. Comb Chem High Throughput Screen 2022; •••
[http://dx.doi.org/10.2174/1386207325666220609120001] [PMID: 35692140]
[12]
Xia B, Zhang K, Liu C. PYGB promoted tumor progression by regulating Wnt/β-catenin pathway in gastric cancer. Technol Cancer Res Treat 2020; 19
[http://dx.doi.org/10.1177/1533033820926592] [PMID: 32462986]
[13]
Akrami H, Moradi B, Borzabadi Farahani D, Mehdizadeh K. Ibuprofen reduces cell proliferation through inhibiting Wnt/β catenin signaling pathway in gastric cancer stem cells. Cell Biol Int 2018; 42(8): 949-58.
[http://dx.doi.org/10.1002/cbin.10959] [PMID: 29512256]
[14]
Yu J, Peng W, Xue Y, Li Y, Yang L, Geng Y. FUBP1 promotes the proliferation of lung squamous carcinoma cells and regulates tumor immunity through PD-L1. Allergol Immunopathol (Madr) 2022; 50(5): 68-74.
[http://dx.doi.org/10.15586/aei.v50i5.659] [PMID: 36086966]
[15]
Zhang F, Guo J, Yu S, Zhao X, Ma Y, Yang D. Huwe1 inactivation promotes ovarian cancer metastasis by extracellular matrix deregulation. Eur J Gynaecol Oncol 2022; 43(1): 48-55.
[http://dx.doi.org/10.31083/j.ejgo4301013]
[16]
Chen L, Wang X, Zhu Y, Liu F, Liu L, Jiang N. Effects of miR-211-3p/RHBDD1 axis on cell proliferation, cell cycle progression, and epithelial-mesenchymal transition in glioma. Folia Neuropathol 2022; 60(2): 195-209.
[http://dx.doi.org/10.5114/fn.2022.118186] [PMID: 35950472]
[17]
Jin X, Jin W, Li G, Zheng J. Zeaxanthin attenuates OVA-induced allergic asthma in mice by regulating the p38 MAPK/β-catenin signaling pathway. Allergol Immunopathol (Madr) 2022; 50(5): 75-83.
[http://dx.doi.org/10.15586/aei.v50i5.664] [PMID: 36086967]
[18]
Wang H, Chen X, Yang B, Xia Z, Chen Q. MiR-924 as a tumor suppressor inhibits non-small cell lung cancer by inhibiting RHBDD1/Wnt/β-catenin signaling pathway. Cancer Cell Int 2020; 20(1): 491.
[http://dx.doi.org/10.1186/s12935-020-01516-0] [PMID: 33041671]
[19]
Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: Clinical update. Nat Rev Clin Oncol 2015; 12(8): 445-64.
[http://dx.doi.org/10.1038/nrclinonc.2015.61] [PMID: 25850553]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy