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J Cancer 2023; 14(14):2739-2750. doi:10.7150/jca.86718 This issue Cite

Research Paper

A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer

Jia-Ke Li1, Hai Liu1, Hui-Wen Zhang1, Jun Li1, Zhuo-Tao Liang2✉

1. Department of General Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.
2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

✉ Corresponding author: Zhuo-Tao Liang (liangztedu.cn), National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Citation:
Li JK, Liu H, Zhang HW, Li J, Liang ZT. A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer. J Cancer 2023; 14(14):2739-2750. doi:10.7150/jca.86718. https://www.jcancer.org/v14p2739.htm
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Abstract

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Purpose: Colorectal cancer (CRC) is the 3rd most prevalent malignant tumour globally. Although significant strides have been made in diagnosis and treatment, its prognosis at the moment remains unpromising. Therefore, there is an urgent and desperate need to identify novel biomarkers of CRC and evaluate its mechanism of tumourigenesis and development.

Methods: JASPAR and RNAinter databases are used to analyze target genes associated with colorectal cancer. Western blotting, q-PCR and immunohistochemistry et, al. were used to detect the level of MNX1 in patients with colorectal cancer, and Chip-PCR was used to detect the targeted binding ability of E2F4 and MNX1. The cells and animal models overexpressed MNX1 and E2F4 were constructed by shRNA transfection.

Results: Herein, MNX1 was highly expressed and linked to favourable overall survival curves in colorectal cancer. The functional assay revealed that MNX1 overexpression could promote proliferation, migration, and invasion of CRC cells. Based on the prediction of the JASPAR and RNAinter databases, the transcription factor, E2F4, was bound to the MNX1 promoter region. The Chromatin Immunoprecipitation (ChIP) assay verified the interactions between MNX1 and E2F4 in CRC. Additionally, we found that sh-E2F4 markedly downregulated the MNX1 levels and reduced CRC progression in vivo and in vitro, which reversed MNX1 overexpression.

Conclusion: Therefore, our research discovered that E2F4-mediated abnormal MNX1 expression promotes CRC progression and could become a novel diagnostic or therapeutic target of CRC.

Keywords: MNX1, E2F4, Colorectal Cancer (CRC), diagnostic biomarker

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APA
Li, J.K., Liu, H., Zhang, H.W., Li, J., Liang, Z.T. (2023). A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer. Journal of Cancer, 14(14), 2739-2750. https://doi.org/10.7150/jca.86718.

ACS
Li, J.K.; Liu, H.; Zhang, H.W.; Li, J.; Liang, Z.T. A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer. J. Cancer 2023, 14 (14), 2739-2750. DOI: 10.7150/jca.86718.

NLM
Li JK, Liu H, Zhang HW, Li J, Liang ZT. A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer. J Cancer 2023; 14(14):2739-2750. doi:10.7150/jca.86718. https://www.jcancer.org/v14p2739.htm

CSE
Li JK, Liu H, Zhang HW, Li J, Liang ZT. 2023. A Positive Feedback Loop of E2F4-Mediated Activation of MNX1 Regulates Tumour Progression in Colorectal Cancer. J Cancer. 14(14):2739-2750.

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