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Altered expression level of Sigma1 receptor gene in human colorectal cancer
Michał Skrzycki1, Hanna Czeczot
1Department of Biochemistry, Warsaw Medical University , Warsaw , Poland.
Abstract:
Nonopioid Sigma1 receptor (Sig1R) influences numerous metabolism functions including regulation of ion channels, reaction on stress and response to growth signals. Due to this influence, Sigma1 receptor ligands show anti-proliferative and cytotoxic action on tumor cells. Additionally its increased level is observed in some types of tumors. Colorectal cancer is one of the most common cancers worldwide and its clinical development is well described. The aim of the study was evaluation of Sigma1 receptor mRNA expression level in human colorectal cancer and colorectal cancer liver metastases at different stages of tumor development. The mRNA was isolated from 30 patients: 18 with colorectal cancer (CRC) and 12 with colorectal cancer liver metastases (CRCLM). The cDNA of Sig1R gene was amplified by polymerase chain reaction using specific primers. The level of Sig1R mRNA expression was determined by measurement of optical density. Sig1R expression level was increased in CRC and CRCLM. The highest level of Sig1R mRNA was observed in UICC stage III. We also showed significant interactions of UICC stage and tumor localization with Sig1R expression level. There were no interactions between UICC stage and age of patients, although we observed significantly decreased level of Sig1R mRNA in older patients. Clinical advancement stage, localization of tumor and age of patients seems to be an important factors influencing Sigma1 receptor expression level. It is probably due to double nature of Sig1R action - in certain conditions it could act pro- or antiapoptotic. This action might depend on Sig1R activity resulting from its expression level.
Insights
Sigma1 receptor (Sig1R) mRNA expression is elevated in colorectal cancer and liver metastases, particularly in advanced stages. Sig1R levels are influenced by tumor stage, location, and patient age, suggesting a role in cancer progression.
Area of Science:
- Molecular biology
- Oncology
- Biochemistry
Background:
- The nonopioid Sigma1 receptor (Sig1R) regulates cellular functions like ion channel activity, stress response, and growth signaling.
- Sig1R ligands exhibit anti-proliferative and cytotoxic effects on tumor cells, and its expression is often upregulated in various cancers.
Purpose of the Study:
- To investigate the messenger RNA (mRNA) expression level of the Sigma1 receptor in human colorectal cancer (CRC) and its liver metastases (CRCLM) across different clinical stages.
Main Methods:
- Messenger RNA (mRNA) was extracted from 30 patients (18 CRC, 12 CRCLM).
- Sigma1 receptor gene cDNA was amplified using polymerase chain reaction (PCR) with specific primers.
- Sig1R mRNA expression levels were quantified by measuring optical density.
Main Results:
- Sigma1 receptor mRNA expression was found to be increased in both colorectal cancer and liver metastases.
- The highest Sig1R mRNA levels were observed in patients with UICC stage III tumors.
- Significant correlations were identified between Sig1R expression levels, tumor stage (UICC), and tumor localization. A decrease in Sig1R mRNA was noted in older patients.
Conclusions:
- Sigma1 receptor expression is elevated in colorectal cancer and liver metastases, with levels varying by clinical stage, tumor location, and patient age.
- These factors appear to influence the Sigma1 receptor's expression, potentially modulating its dual pro- or anti-apoptotic roles in cancer.
- Further research into Sig1R's activity based on expression levels is warranted for understanding its role in colorectal cancer progression.
