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


Дәйексөз келтіру

Толық мәтін

Аннотация

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.

Негізгі сөздер

Авторлар туралы

Paerhati Shayimu

Department of Gastrointestinal Surgery, Affiliated Tumor Hospital of Xinjiang Medical University

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Cheng Yin

Department of Major Surgery, The Sixth Division Hospital of Xinjiang Corps

Email: info@benthamscience.net

Xiangyue Zeng

Department of Gastrointestinal Surgery,, Affiliated Tumor Hospital of Xinjiang Medical University

Email: info@benthamscience.net

Rexida Jiapaer

Department of Color Doppler diagnostic,, Affiliated Tumor Hospital of Xinjiang Medical University

Email: info@benthamscience.net

Әдебиет тізімі

  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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 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. doi: 10.1158/1078-0432.CCR-10-2816 PMID: 22042972

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