Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

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

Research Article

Knockdown of VASH2 Inhibits the Stemness and EMT Process by Regulating ZEB2 in Colorectal Cancer

Author(s): Paerhati Shayimu*, Cheng Yin, Xiangyue Zeng and Rexida Jiapaer

Volume 19, Issue 1, 2024

Published on: 08 May, 2023

Page: [126 - 132] Pages: 7

DOI: 10.2174/1574888X18666230417084221

Price: $65

Abstract

Introduction: VASH2 is associated with the malignant progression of a variety of tumors, but the role and mechanism of VASH2 in colorectal cancer are still unclear.

Methods: We analyzed the expression of VASH2 in colorectal cancer from the TCGA database and also analyzed the relationship between VASH2 expression and survival of colorectal cancer patients in the PrognoScan database. We verified the role of VASH2 in colorectal cancer through transfecting si-VASH2 into colorectal cancer cells and detecting cell viability by CCK8, cell migration by wound healing assay, and cell invasion by Transwell assay. ZEB2, Vimentin, and E- cadherin protein expression were examined by Western-Blot assay. Cell sphere-forming ability was determined by sphere formation assay, and we further confirmed the mechanism of VASH2 in colorectal cancer progression by rescue assays.

Results: Colorectal cancer has a high expression of VASH2, and its expression is associated with a poorer patient survival rate. The vitality, migration, invasion, EMT, and tumor stemness of colorectal cancer cells were all decreased by VASH2 knockdown. These alternations were attenuated by ZEB2 overexpression.

Conclusion: Our experiments confirmed that VASH2 affects colorectal cancer cell proliferation, migration, invasion, EMT, and seed bovine stemness by regulating ZEB2 expression.

Graphical Abstract

[1]
Yang B, Bai H, Sa Y, Zhu P, Liu P, Inhibiting EMT. Inhibiting EMT, stemness and cell cycle involved in baicalin-induced growth inhibition and apoptosis in colorectal cancer cells. J Cancer 2020; 11(8): 2303-17.
[http://dx.doi.org/10.7150/jca.37242] [PMID: 32127957]
[2]
Tang X, Zha L, Li H, et al. Upregulation of GNL3 expression promotes colon cancer cell proliferation, migration, invasion and epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway. Oncol Rep 2017; 38(4): 2023-32.
[http://dx.doi.org/10.3892/or.2017.5923] [PMID: 28849076]
[3]
Shayimu P, Yusufu A, Rehemutula A, Redati D, Jiapaer R, Tuerdi R. MicroRNA-377 counteracts with cancer stem cell phenotypes and epithelial mesenchymal transformation by targeting ZEB2 in colon cancer. Technol Cancer Res Treat 2020; 19: 1533033820967475.
[http://dx.doi.org/10.1177/1533033820967475] [PMID: 33084522]
[4]
Sato Y, Sonoda H. The vasohibin family: A negative regulatory system of angiogenesis genetically programmed in endothelial cells. Arterioscler Thromb Vasc Biol 2007; 27(1): 37-41.
[http://dx.doi.org/10.1161/01.ATV.0000252062.48280.61] [PMID: 17095714]
[5]
Li Z, Tu M, Han B, et al. Vasohibin 2 decreases the cisplatin sensitivity of hepatocarcinoma cell line by downregulating p53. PLoS One 2014; 9(3): e90358.
[http://dx.doi.org/10.1371/journal.pone.0090358] [PMID: 24595063]
[6]
Tu M, Li H, Lv N, et al. Vasohibin 2 reduces chemosensitivity to gemcitabine in pancreatic cancer cells via Jun proto-oncogene dependent transactivation of ribonucleotide reductase regulatory subunit M2. Mol Cancer 2017; 16(1): 66.
[http://dx.doi.org/10.1186/s12943-017-0619-6] [PMID: 28327155]
[7]
Ninomiya Y, Ozawa S, Oguma J, et al. Expression of vasohibin-1 and -2 predicts poor prognosis among patients with squamous cell car-cinoma of the esophagus. Oncol Lett 2018; 16(4): 5265-74.
[http://dx.doi.org/10.3892/ol.2018.9249] [PMID: 30250596]
[8]
Xue X, Zhang Y, Zhi Q, et al. MiR200-upregulated Vasohibin 2 promotes the malignant transformation of tumors by inducing epithelial-mesenchymal transition in hepatocellular carcinoma. Cell Commun Signal 2014; 12(1): 62.
[http://dx.doi.org/10.1186/s12964-014-0062-x] [PMID: 25269476]
[9]
Shayimu P, Yusufu A, Rehemutula A, Redati D, Jiapaer R, Tuerdi R. MTBP promoted the proliferation, migration and invasion of colon cancer cells by activating the expression of ZEB2. Anim Cells Syst 2021; 25(3): 152-60.
[http://dx.doi.org/10.1080/19768354.2021.1938218] [PMID: 34262658]
[10]
Sun S, Yang X, Qin X, Zhao Y. TCF4 promotes colorectal cancer drug resistance and stemness via regulating ZEB1/ZEB2 expression. Protoplasma 2020; 257(3): 921-30.
[http://dx.doi.org/10.1007/s00709-020-01480-6] [PMID: 31933004]
[11]
Li N, Babaei-Jadidi R, Lorenzi F, et al. An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance. Oncogenesis 2019; 8(3): 13.
[http://dx.doi.org/10.1038/s41389-019-0125-3] [PMID: 30783098]
[12]
Koyanagi T, Suzuki Y, Saga Y, et al. In vivo delivery of siRNA targeting vasohibin-2 decreases tumor angiogenesis and suppresses tumor growth in ovarian cancer. Cancer Sci 2013; 104(12): 1705-10.
[http://dx.doi.org/10.1111/cas.12297] [PMID: 24118388]
[13]
Tian Y, Xu T, Huang J, et al. Tissue metabonomic phenotyping for diagnosis and prognosis of human colorectal cancer. Sci Rep 2016; 6(1): 20790.
[http://dx.doi.org/10.1038/srep20790] [PMID: 26876567]
[14]
Tan X, Liao Z, Zou S, Ma L, Wang A. VASH2 promotes cell proliferation and resistance to doxorubicin in non-small cell lung cancer via AKT signaling. Oncol Res 2020; 28(1): 3-11.
[http://dx.doi.org/10.3727/096504019X15509383469698] [PMID: 30940294]
[15]
Pan G, Liu Y, Shang L, Zhou F, Yang S. EMT‐associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun 2021; 41(3): 199-217.
[http://dx.doi.org/10.1002/cac2.12138] [PMID: 33506604]
[16]
Chen N, Han X, Bai X, Yin B, Wang Y. LASP1 induces colorectal cancer proliferation and invasiveness through Hippo signaling and Nanog mediated EMT. Am J Transl Res 2020; 12(10): 6490-500.
[PMID: 33194046]
[17]
Zhu Y, Huang S, Chen S, et al. SOX2 promotes chemoresistance, cancer stem cells properties, and epithelial-mesenchymal transition by β-catenin and Beclin1/autophagy signaling in colorectal cancer. Cell Death Dis 2021; 12(5): 449.
[http://dx.doi.org/10.1038/s41419-021-03733-5] [PMID: 33953166]
[18]
Zhu Y, Wang C, Becker SA, et al. miR-145 antagonizes SNAI1-mediated stemness and radiation resistance in colorectal cancer. Mol Ther 2018; 26(3): 744-54.
[http://dx.doi.org/10.1016/j.ymthe.2017.12.023] [PMID: 29475734]
[19]
Wang B, Yang L, Zhao Q, Zhu L. Vasohibin 2 as a potential predictor of aggressive behavior of triple-negative breast cancer. Am J Transl Res 2017; 9(6): 2911-9.
[PMID: 28670379]
[20]
Norita R, Suzuki Y, Furutani Y, et al. Vasohibin-2 is required for epithelial-mesenchymal transition of ovarian cancer cells by modulating transforming growth factor-β signaling. Cancer Sci 2017; 108(3): 419-26.
[http://dx.doi.org/10.1111/cas.13157] [PMID: 28064471]
[21]
Kahlert C, Lahes S, Radhakrishnan P, et al. Overexpression of ZEB2 at the invasion front of colorectal cancer is an independent prognostic marker and regulates tumor invasion in vitro. Clin Cancer Res 2011; 17(24): 7654-63.
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2816] [PMID: 22042972]

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