EZH2 Gene Silencing Can Affect the Expression of miR-155 and TP53INP1

Document Type : Research Articles

Author

• Madjid Momeni-Moghaddam

Hakim Sabzevari University, Sabzevar, Iran

https://doi.org/10.22067/jcmr.v11i1.82685

Abstract

Many genetic, epigenetic, and cellular studies on cancer are underway today, and the completion of the genetic and epigenetic library of cancer could be the way to treat the disease in the future. In this study, we have investigated the parallel gene expression changes of EZH2 and miR-155. So far no study has examined the role of these two factors simultaneously and the results of this study could be useful for further studies. For this purpose, using specific shRNA, the EZH2 gene of HCT116 cells was downregulated and then the changes in expression of the miR-155 were investigated. For gene expression study, Real-time PCR as a standard quantitative method was used. The findings of this study showed that in HCT116 human colon cancer cells, downregulation of miR-155 using shRNA can reduce EZH2 expression and also can promote a significant increase in the expression of TP53INP1 gene. Based on the results, we can emphasize the interaction between these two genes. Importantly, EZH2 downregulation has been able to decrease the amount of miR-155 that has also increased expression in many types of cancers. It may be of interest in epigenetic treatments of colon cancer, because miR-155 can control a very important tumor suppressor gene, TP53INP1.

Keywords

• 1
• colorectal cancer
• EZH2
• miR-155
• epigenetic
• HCT116 cell line

20.1001.1.20089147.2019.11.1.5.4

References

Bouamar, Hakim, Daifeng Jiang, Long Wang, An-Ping Lin, Manoela Ortega, and Ricardo C T Aguiar. (2015) MicroRNA 155 Control of P53 Activity Is Context Dependent and Mediated by Aicda and Socs1. Molecular and Cellular Biology 35 (8): 1329–40.

Chen, Jian-Fang, Xi Luo, Li-Sha Xiang, Hong-Tao Li, Lin Zha, Ni Li, Jian-Ming He, Gan-Feng Xie, Xiong Xie, and Hou-Jie Liang. (2016) EZH2 Promotes Colorectal Cancer Stem-like Cell Expansion by ActivatingP21cip1-Wnt/β-Catenin Signaling.” Oncotarget 7 (27): 41540–58.

Chen, Zhuanpeng, Ping Yang, Wanglin Li, Feng He, Jianchang Wei, Tong Zhang, Junbin Zhong, Huacui Chen, and Jie Cao. (2018) Expression of EZH2 Is Associated with Poor Outcome in Colorectal Cancer. Oncology Letters 15 (3): 2953–61.

Das, L M, M D L A Torres-Castillo, T Gill, and A D Levine. (2013) TGF-β Conditions Intestinal T Cells to Express Increased Levels of MiR-155, Associated with down-Regulation of IL-2 and Itk MRNA. Mucosal Immunology 6 (1): 167–76.

Etna, Marilena P, Alessandro Sinigaglia, Angela Grassi, Elena Giacomini, Alessandra Romagnoli, Manuela Pardini, Martina Severa, et al. (2018) Mycobacterium Tuberculosis-Induced MiR-155 Subverts Autophagy by Targeting ATG3 in Human Dendritic Cells. PLoS Pathogens 14 (1): e1006790–e1006790.

Farnia Ghafouri Sabzevari, Madjid Momeni-Moghaddam, Faris Farassati and Abolfazl Rad. (2014) Effect of EZH2 Inhibition on Colorectal Cancer Cells: An In Vitro Study 6 (8): 289–300.

Jiang, Mingzuo, Bing Xu, Xiaowei Li, Yulong Shang, Yi Chu, Weijie Wang, Di Chen, et al. (2019) O-GlcNAcylation Promotes Colorectal Cancer Metastasis via the MiR-101-O-GlcNAc/EZH2 Regulatory Feedback Circuit. Oncogene 38 (3): 301–16.

Kuipers, Ernst J, William M Grady, David Lieberman, Thomas Seufferlein, Joseph J Sung, Petra G Boelens, Cornelis J H van de Velde, and Toshiaki Watanabe. (2015) Colorectal Cancer. Nature Reviews. Disease Primers 1 (November): 15065.

Li, Ning, Tao Cui, Wenling Guo, Dianwei Wang, and Li Mao. (2019) MiR-155-5p Accelerates the Metastasis of Cervical Cancer Cell via Targeting TP53INP1. OncoTargets and Therapy 12 (April): 3181–96.

Li, Yang, Yanhong Duo, Jiangang Bi, Xiaowei Zeng, Lin Mei, Shiyun Bao, Lisheng He, Aijun Shan, Yue Zhang, and Xiaofang Yu. (2018) Targeted Delivery of Anti-MiR-155 by Functionalized Mesoporous Silica Nanoparticles for Colorectal Cancer Therapy. International Journal of Nanomedicine 13 (March): 1241–56.

Lin, Xiaolin, Yujuan Qin, Junshuang Jia, Taoyan Lin, Xia Lin, Li Chen, Hui Zeng, et al. (2016) MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice. PLoS Genetics 12 (10): e1006308–e1006308.

Liu, Yongfeng, Junjie Peng, Tongyu Sun, Ni Li, Le Zhang, Jiale Ren, Huairui Yuan, et al. (2017) Epithelial EZH2 Serves as an Epigenetic Determinant in Experimental Colitis by Inhibiting TNFα-Mediated Inflammation and Apoptosis. Proceedings of the National Academy of Sciences of the United States of America 114 (19): E3796–3805.

Lui, Julian C, Kevin M Barnes, Lijin Dong, Shanna Yue, Evan Graber, Robert Rapaport, Andrew Dauber, Ola Nilsson, and Jeffrey Baron. (2018) Ezh2 Mutations Found in the Weaver Overgrowth Syndrome Cause a Partial Loss of H3K27 Histone Methyltransferase Activity. The Journal of Clinical Endocrinology and Metabolism 103 (4): 1470–78.

Momeni-Moghaddam, Madjid, Elnaz Yossefi, and Fatemeh Oladi. (2017). MicroRNAs: Small Regulators of Tissue Regeneration. Journal of Genes and Cells 3 (1): 6.

Qiu, Lipeng, Yan Zhang, Danh C Do, Xia Ke, Simin Zhang, Kristin Lambert, Shruthi Kumar, et al. (2018) MiR-155 Modulates Cockroach Allergen- and Oxidative Stress-Induced Cyclooxygenase-2 in Asthma. Journal of Immunology (Baltimore, Md. : 1950) 201 (3): 916–29.

Ragusa, Marco, Cristina Barbagallo, Luisa Statello, Angelo Giuseppe Condorelli, Rosalia Battaglia, Lucia Tamburello, Davide Barbagallo, Cinzia Di Pietro, and Michele Purrello. (2015) Non-Coding Landscapes of Colorectal Cancer.” World Journal of Gastroenterology 21 (41): 11709–39.

Seillier, M, S Peuget, O Gayet, C Gauthier, P N’Guessan, M Monte, A Carrier, J L Iovanna, and N J Dusetti. (2012) TP53INP1, a Tumor Suppressor, Interacts with LC3 and ATG8-Family Proteins through the LC3-Interacting Region (LIR) and Promotes Autophagy-Dependent Cell Death. Cell Death and Differentiation 19 (9): 1525–35.

Shojania, Hamid Reza, Madjid Momeni-moghaddam, Seyed-ebrahim Hossini, Mohammad Armin, and Jalal Omrani Bidi. (2019) MicroRNA 155 Downregulation by Vitamin C – Loaded Human Serum Albumin Nanoparticles During Cutaneous Wound Healing in Mice. The International Journal of Lower Extremity Wounds.

Teymoori, Atieh, Mojtaba Teimoori, and Madjid Momeni-moghaddam. (2017) Non-Coding RNAs Could Be New Tools for Cancer Treatment. Journal of Cell and Molecular Research 9: 44–53.

Yu, San-Jian, Liu Yang, Qi Hong, Xia-Ying Kuang, Gen-Hong Di, and Zhi-Ming Shao. (2018) MicroRNA-200a Confers Chemoresistance by Antagonizing TP53INP1 and YAP1 in Human Breast Cancer.” BMC Cancer 18 (1): 74.

Zhang, Chun-Mei, Jing Zhao, and Hua-Yu Deng. (2013) MiR-155 Promotes Proliferation of Human Breast Cancer MCF-7 Cells through Targeting Tumor Protein 53-Induced Nuclear Protein 1. Journal of Biomedical Science 20 (1): 79.

Zhou, Xinru, Yong Mao, Jianjie Zhu, Fanyi Meng, Qi Chen, Lihua Tao, Rui Li, et al. (2016) TGF-Β1 Promotes Colorectal Cancer Immune Escape by Elevating B7-H3 and B7-H4 via the MiR-155/MiR-143 Axis. Oncotarget 7 (41): 67196–211.