Uncovering tumor markers of colorectal cancer is important for the early detection and prognosis of the patients. Spermine oxidase (SMOX) is upregulated in various cancers. The present study aims to explore the biologic function and expression patterns of SMOX in colorectal cancer (CRC), the third most common type of cancer worldwide. We used quantitative real-time PCR, Western blot, and in vitro functional studies in four CRC cell lines knocked down by SMOX siRNA and immunohistochemistry in 350 cases of CRC tissues. The results showed that SMOX was overexpressed in CRC cell lines and clinical samples. SMOX overexpression in tumor tissues was an independent prognostic factor, worsening overall survival (p = 0.001). The knock-down of SMOX inhibited CRC cell proliferation, invasion, and soft agar colony formation, uncovering its carcinogenic functions. This study indicated that SMOX overexpression could be an important oncogene in CRC and might serve as a valuable prognostic marker and potential therapeutic target for CRC.
Cancer is a major disease and the leading cause of death worldwide, with colorectal cancer (CRC) being the third-most common cancer in Korea. The survival rate associated with CRC reduces as the disease stage increases. Therefore, its early detection and treatment can greatly increase patient survival rates. In this study, we identified the tetraspanin 5 (TSPAN5) gene as an important biomarker for predicting the prognosis of patients with CRC. A TMA slide was used for statistical analysis. pN and clinical stage were found to be significant factors according to chi-square analysis, whereas pT, pN, metastasis, clinical stage, and TSPAN5 expression were significant according to Cox regression analysis. In order to prove the usefulness of TSPAN5, which is overexpressed in patients with metastatic CRC, as a biomarker, proliferation, migration, invasion, and tumorigenicity were examined using cell lines inhibited using small interfering RNA. The evaluations confirmed that TSPAN5 suppression, in turn, suppressed proliferation, migration, invasion, and tumorigenesis, which are characteristic of cancer cells. Therefore, the evaluation of TSPAN5 expression may help observe the prognosis of CRC and determine an appropriate treatment method for patients with CRC.
Colorectal cancer (CRC) is common cancer worldwide, and the 5-year relative survival rate of CRC patients with distant metastasis is as low as 14%. Therefore, identifying markers of CRC is important for the early detection of CRC and applying appropriate treatment strategies. The lymphocyte antigen 6 family (LY6 family) is closely related to the behavior of various cancer types. Among the LY6 family, the lymphocyte antigen 6 complex, locus E (LY6E), which is specifically highly expressed in CRC. Hence, the effects of LY6E on cell function in CRC and its role in CRC recurrence and metastasis were investigated. Reverse transcription-quantitative PCR, western blotting and in vitro functional studies were carried out using four CRC cell lines. Immunohistochemical analysis of 110 CRC tissues was performed to explore the biological functions and expression patterns of LY6E in CRC. LY6E was overexpressed CRC tissues compared with that in adjacent normal tissues. High expression of LY6E in CRC tissues was an independent prognostic factor of worse overall survival (P=0.048). Knockdown of LY6E using small interfering RNA inhibited CRC cell proliferation, migration, invasion, and soft agar colony formation, indicating some of its effects on CRC carcinogenic functions. High expression of LY6E may have oncogenic functions in CRC and be useful as a valuable prognostic marker and potential therapeutic target for CRC.
Background Colorectal cancer (CRC) is the third most common cancer and has the second highest mortality rate. The recurrence rate of colorectal cancer is 30–50%, and the survival rate of patients with recurrence and metastasis is very low. Prognostic biomarkers of colorectal cancer can be guidelines for the therapeutic management of the cancer patients. The cytochrome P450 (CYP) family is upregulated in various cancers and contributes to cancer cell proliferation, signaling and drug metabolism. In addition, the Cytochrome P450 family is related to various xenobiotics and endogenous compounds. Nevertheless, the role of CYP4X1 in regulating the progression and growth of colorectal cancer remains unclear. Methods To investigate the relationship between CYP4X1 expression and colorectal cancer, CYP4X1 expression was inhibited in colorectal cancer cells using siRNA and confirmed at mRNA and protein levels. WST-1, Transwell and colony formation assays were performed using CYP4X1 downregulated cells. We performed immunohistochemistry for the CYP4X1 expression of 243 colorectal cancer tissues and investigated the expression with the patient’s clinical parameters. Results In colorectal cancer, downregulated CYP4X1 suppressed proliferation, migration, invasion, and colony formation. CYP4X1 overexpression was found to be related to TNM stage, degree of tumor differentiation, invasion of the primary tumor, clinical stages, and lymph node metastasis. In addition, the high CYP4X1 expression revealed a shorter survival period than those with low CYP4X1 expression by Kaplan-Meier survival analysis. Conclusions Upregulated CYP4X1 may be an independent prognostic marker for CRC, and CYP4X1 may be a therapeutic target for CRC patients. Epoxyeicosatrienoic acid (EET) derived from arachidonic acid has been implicated in carcinogenesis due to its CYP polymorphism. Whether CYP4X1 regulates EET in CRC remains unknown. Therefore, the increased CYP4X1 in EET requires further studies on the correlation between EGFR phosphorylation and PI3K/AKT and MAPK signaling.
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