Expression Levels of the YAP, TAZ, and TEAD1 Hippo Pathway Genes in Colorectal Villous Adenoma Polyps

Document Type : Research/Original Article

Authors

Department of biotechnology, Tehran university of Medical Sciences, Tehran, Iran

Abstract

Background
Villous adenoma polyps are mostly considered to associate with a high risk for colorectal cancer (CRC) development. Hippo signaling pathway role have been investigated in CRC by regulating cell proliferation and apoptosis, however, the role of this pathway in different adenoma polyps and its relationship to CRC development is not fully discovered yet.
Methods:
Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the mRNA expression levels of, YAP, TAZ, TEAD1 in 30 pairs of villous adenomas polyps’ tissues, and adjacent normal tissues. In addition, the correlation between clinicopathologic features and the YAP, TAZ, and TEAD1 expression in villous adenoma polyps’ patients and ROC curve analyses were evaluated in this study.
Results:
The mRNA expression levels of YAP, TAZ, and TEAD were found to be overexpressed in villous adenoma polyps’ tissues compared to adjacent normal tissues (**P < 0.01, ****P <0.0001). statistical analysis showed that the expression levels of YAP, TAZ, and TEAD were associated with lymph node metastasis while only TAZ was associated with the TNM stage (I-II). Moreover, YAP, TAZ, and TEAD may have the potential to distinguish villous adenoma polyps from the adjacent normal tissues by the large area under the ROC curve (0.74, 0.70, 0.68, respectively).
Conclusion:
Our study highlights that the upregulation of YAP, TAZ, and TEAD genes in the Hippo pathway can affect the progression of villous adenoma polyps to CRC and can be a potential target for further investigation of a novel biomarker for patients with villous adenoma polyps.

Keywords


  1. Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, et al. Colorectal cancer statistics, 2020. CA Cancer J Clin [Internet]. 2020 May [cited 2021 Feb 16];70(3):145–64.
  2. Gausachs M, Borras E, Chang K, Gonzalez S, Azuara D, Amador AD, et al. Mutational heterogeneity in APC and KRAS arises at the crypt level and leads to polyclonality in early colorectal tumorigenesis. Clin Cancer Res [Internet]. 2017 Oct 1.
  3. [cited 2021 Apr 11];23(19):5936–47. Available from: https://pubmed.ncbi. nlm.nih.gov/28645942/3. Barbie D. Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1.Nature. 2009 Nov 5;462(7269):108–12.
  4. Shussman N, Wexner SD. Colorectal polyps and polyposis syndromes. Gastroenterol Rep [Internet]. 2014 Feb 1 [cited 2021 Aug 24];2(1):1.
  5. AmeliMojarad M, wang jian, Mojarad MA. The function of novel small non‐coding RNAs (piRNAs, tRFs) and PIWI protein in colorectal cancer. Cancer Treat Res Commun [Internet]. 2022 Mar 1 [cited 2022 Mar 1];100542.
  6. AmeliMojarad M, AmeliMojarad M, Pourmahdian A. Circular RNA circ_0051620 sponges miR-338-3p and regulates ADAM17 to promote the gastric cancer progression. Pathol Res Pract [Internet]. 2022 May [cited 2022 Apr 17];233:153887.
  7. Laiyemo AO, Murphy G, Sansbury LB, Wang Z, Albert PS, Marcus PM, et al. Hyperplastic polyps and the risk of adenoma recurrence in the Polyp Prevention Trial. Clin Gastroenterol Hepatol [Internet]. 2009 Feb [cited 2021 Aug 24];7(2):192.
  8. Amersi F, Agustin M, Ko CY. Colorectal Cancer: Epidemiology, Risk Factors, and Health Services. Clin Colon Rectal Surg [Internet]. 2005 Aug [cited 2021 Aug 25];18(3):133.
  9. Mojarad MA, Mojarad MA. piRNAs and PIWI proteins as potential biomarkers in colorectal cancer. J Clin Images Med Case Reports. 2021;2(6).
  10. liang, Zhou G, Zhang Q, Li J, Zhang C. Expression of hippo pathway in colorectal cancer. Saudi J Gastroenterol [Internet]. 2014 [cited 2021 Aug 24];20(3):188.
  11. Boopathy GTK, Hong W. Role of Hippo Pathway-YAP/TAZ Signaling in Angiogenesis. Front Cell Dev Biol. 2019;0(APR):49.
  12. Zhao B, Wei X, Li W, Udan R, … QY-G&, 2007 undefined. Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control .genesdev.cshlp.org [Internet].[cited 2021 Aug 25].
  13. Mouillet-Richard S, Laurent-Puig P. YAP/TAZ signalling in colorectal cancer: Lessons from consensus molecular subtypes. Vol. 12, Cancers. MDPI AG; 2020. p. 1–18.
  14. Lin L, Sabnis AJ, Chan E, Olivas V, Cade L, Pazarentzos E, et al. The Hippo effector YAP promotes resistance to RAF- and MEKtargeted cancer therapies. Nat Genet [Internet]. 2015 Feb 25 [cited 2021 Jun 2];47(3):250–6.
  15. Hansen CG, Moroishi T, Guan KL. YAP and TAZ: A nexus for Hippo signaling and beyond [Internet]. Vol. 25, Trends in Cell Biology. Elsevier Ltd; 2015 [cited 2021 Jun 2]. p. 499–513. 
  16. Konsavage WM, Kyler SL, Rennoll SA, Jin G, Yochum GS. Wnt/β-catenin signaling regulates yes-associated protein (YAP) gene expression in colorectal carcinoma cells. J Biol Chem [Internet]. 2012 Apr 6 [cited 2021 Jun 2];287(15):11730–9.
  17. Zhou Z, Hao Y, Liu N, Raptis L, Tsao MS, Yang X. TAZ is a novel oncogene in non-small cell lung cancer. Oncogene [Internet]. 2011 May 5 [cited 2021 Jun 2];30(18):2181–6.
  18. Zhou X, Lei Q-Y. Regulation of TAZ in cancer. Protein Cell [Internet]. 2016 Aug 1 [cited 2021 Aug 24];7(8):548.
  19. MH Y, W Z. TEAD1 enhances proliferation via activating SP1 in colorectal cancer. Biomed Pharmacother [Internet]. 2016 Oct 1 [cited 2021 Aug 23];83:496–501.
  20. Amelimojarad M, AmeliMojarad M. Circ-ADAM9: a novel biomarker in human cancers. Cancer Adv[Internet]. 2022 [cited 2022 Jan10];5(0):e22001.
  21. Cancers | Special Issue : Hippo Signaling Pathway in Cancers [Internet]. [cited 2021 Jun 10].
  22. Zhou D, Zhang Y, Wu H, Barryg E, Yin Y, Lawrence E, et al. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A [Internet]. 2011 Dec 6 [cited 2021 Jun 2];108(49).                                                                               
  23. Yuen HF, McCrudden CM, Huang YH, Tham JM, Zhang X, Zeng Q, et al. TAZ Expression as a Prognostic Indicator in Colorectal Cancer. PLoS One [Internet]. 2013 Jan 29 [cited 2021 Jun 2];8(1).
  24. Kim GJ, Kim H, Park YN. Increased Expression of Yes-Associated Protein 1 in Hepatocellular Carcinoma with Stemness and Combined Hepatocellular-Cholangiocarcinoma. PLoS One. 2013 Sep 24;8(9).
  25. Article R. Clinical Images and Medical Case Reports piRNAs and PIWI proteins as potential biomarkers in colorectal cancer.