Abstract
Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.
Highlights
Colorectal cancer (CRC) is the third most commonly diagnosed cancer
We found that the coiled-coil domain containing 80 (CCDC80), a tumor suppressor in CRC, was significantly reduced after NP exposure (Grill et al, 2018)
We found a higher concentration of serum NP in patients with CRC than in healthy individuals in was downregulated and matrix metallopeptidase 19 (MMP19) and SRXN1 were upregulated both men and women (Figure 1)
Summary
Colorectal cancer (CRC) is the third most commonly diagnosed cancer. The relationship between environmental pollution and carcinogens has become a concern. Many studies have demonstrated that EDCs are involved in the occurrence and development of cancers (Marotta et al, 2019; Noorimotlagh et al, 2020; Li et al, 2021). Previous studies have demonstrated that NP could induce female-related cancers, such as breast and ovarian cancers, by binding to nuclear receptors (In et al, 2015; Kim et al, 2015). The relationship between NP exposure and risk of CRC progression has been a concern. Our previous studies have revealed that NP promoted CRC cell proliferation (Xie et al, 2019; Yang et al, 2019). The mechanism of action of NP on CRC progression requires further studies
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