Wu Yung-Fu, Wang Chih-Yang, Tang Wan-Chun, Lee Yu-Cheng, Ta Hoang Dang Khoa, Lin Li-Chia, Pan Syu-Ruei, Ni Yi-Chun, Anuraga Gangga, Lee Kuen-Haur
National Defense Medical Center, Department of Medical Research, School of Medicine, Tri-Service General Hospital, Taipei 11490, Taiwan.
PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.
Biomedicines. 2021 Sep 27;9(10):1331. doi: 10.3390/biomedicines9101331.
Colorectal cancer (CRC) is a heterogeneous disease with changes in the genetic and epigenetic levels of various genes. The molecular assessment of CRC is gaining increasing attention, and furthermore, there is an increase in biomarker use for disease prognostication. Therefore, the identification of different gene biomarkers through messenger RNA (mRNA) abundance levels may be useful for capturing the complex effects of CRC. In this study, we demonstrate that the high mRNA levels of 10 upregulated genes (, , , , , , , , , and ) are observed in CRC cell lines and public CRC datasets. Moreover, we find that a high mRNA expression of DPEP1, NKD2, CEMIP, ETV4, TESC, or FUT1 is significantly correlated with a worse prognosis in CRC patients. Further investigation reveals that CTNNB1 is the key factor in the interaction of the canonical Wnt signaling pathway with 10 upregulated CRC-associated genes. In particular, we identify , , and as three CTNNB1-regulated genes. Moreover, individual inhibition of the expression of three CTNNB1-regulated genes can cause the growth inhibition of CRC cells. This study reveals efficient biomarkers for the prognosis of CRC and provides a new molecular interaction network for CRC.
结直肠癌(CRC)是一种异质性疾病,其多种基因的遗传和表观遗传水平都发生了变化。CRC的分子评估越来越受到关注,此外,用于疾病预后的生物标志物的使用也在增加。因此,通过信使核糖核酸(mRNA)丰度水平鉴定不同的基因生物标志物可能有助于捕捉CRC的复杂效应。在本研究中,我们证明在CRC细胞系和公开的CRC数据集中观察到10个上调基因(、、、、、、、、和)的mRNA水平较高。此外,我们发现DPEP1、NKD2、CEMIP、ETV4、TESC或FUT1的高mRNA表达与CRC患者较差的预后显著相关。进一步研究表明,CTNNB1是经典Wnt信号通路与10个上调的CRC相关基因相互作用的关键因素。特别是,我们将、和鉴定为三个受CTNNB1调控的基因。此外,单独抑制三个受CTNNB1调控的基因的表达可导致CRC细胞生长受到抑制。本研究揭示了有效的CRC预后生物标志物,并为CRC提供了一个新的分子相互作用网络。