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The KN Motif and Ankyrin Repeat Domains 1/CXXC Finger Protein 5 Axis Regulates Epithelial-Mesenchymal Transformation, Metastasis and Apoptosis of Gastric Cancer via Wnt Signaling

Authors Chen X, Wang X, Yi L, Song Y

Received 3 December 2019

Accepted for publication 12 June 2020

Published 28 July 2020 Volume 2020:13 Pages 7343—7352

DOI https://doi.org/10.2147/OTT.S240991

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai


Xin Chen,1 Xiaodong Wang,1 Lanjuan Yi,2 Ying Song1

1Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin University, Changchun, Jilin 13000, People’s Republic of China; 2Department of Gastroenterology, Yantaishan Hospital of Yantai City, Yantai, Shandong 264000, People’s Republic of China

Correspondence: Ying Song
Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin University, No. 218 Ziqiang Street, Changchun, Jilin 13000, People’s Republic of China
Tel/ Fax +86 431-88796243
Email winvsong@163.com

Background: Emerging research indicates that CXXC finger protein 5 (CXXC5) is involved in the development of various cancers. Besides, KN motif and ankyrin repeat domains 1 (KANK1) was proved as a tumor suppressor in multiple cancers. Our study aimed to illustrate the functional role and mechanism of CXXC5 and KANK1 in gastric cancer (GC) pathogenesis.
Methods: The tissues of 55 GC patients and six GC cell lines were used to investigate CXXC5 and KANK1 expression using RT-qPCR. Western blot assay was conducted to measure the protein levels of CXXC5, KANK1, epithelial-mesenchymal transformation (EMT) proteins (Vimentin, E-cadherin) and Wnt signaling proteins (β-catenin, Axin2). The correlation between KANK1 and CXXC5 was estimated by Pearson’s correlation analysis. The results of Transwell assays showed the migration and invasion abilities of GC cells, while the apoptosis rate was detected by flow cytometry.
Results: The expressions of CXXC5 and KANK1 were both decreased in GC tissues and cells, compared with the normal ones (P < 0.01). Overexpressing CXXC5 significantly induced apoptosis (P < 0.05) and inhibited EMT, migration (P < 0.05) and invasion (P < 0.01) in GC cells. Wnt/β-catenin/Axin2 signaling was suppressed by CXXC5 overexpression, and activating Wnt/β-catenin/Axin2 signaling reversed the effects of CXXC5. The expression of KANK1 was found to be positively correlated with CXXC5 (r2 = 0.4024). KANK1 presented similar effects with CXXC5 on GC cells; however, silencing CXXC5 or activating Wnt/β-catenin/Axin2 signaling antagonized the effects of KANK1 overexpression on EMT and apoptosis in GC (P < 0.05).
Conclusion: Our study suggested that CXXC5 was downregulated in GC and participated in EMT and apoptosis regulations via the Wnt/β-catenin/Axin2 pathway. Besides, the decreased expression of CXXC5 in GC was caused by KANK1 dysregulation.

Keywords: CXXC5, KANK1, EMT, apoptosis, gastric cancer, Wnt/β-catenin/Axin2 signaling

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