Abstract
Immunoglobulin γ-1 heavy chain constant region (IGHG1) is a functional isoform of immunoglobulins and plays an important role in the cytolytic activity of immune effector cells. Dysregulated IGHG1 was implicated in the occurrence and development of various tumors. Protoporphyrin IX (PpIX) is an endogenous fluorophore and is used in photodynamic therapy, which induces the generation of reactive oxygen species to initiate the death of tumor cells. However, the roles of IGHG1 in the colorectal cancer cell proliferation and PpIX accumulation have not been reported yet. Data from qRT-PCR and western blot analysis showed that IGHG1 was up-regulated in the colorectal cancer cells. Colorectal cancer cells were then transfected with shRNA targeting IGHG1 to down-regulate IGHG1 and conducted with Cell Counting Kit 8 (CCK8) and colony formation assays. Results demonstrated that shRNA-mediated down-regulation of IGHG1 decreased cell viability of colorectal cancer and suppressed cell proliferation. Moreover, PpIX accumulation was promoted and the hemin content was decreased by the silence of IGHG1. Interference of IGHG1 reduced the phosphorylated extracellular signal-regulated kinase (ERK) and ferrochelatase (FECH) expression, resulting in retarded cell proliferation in an MEK-FECH axis-dependent pathway.
Highlights
Colorectal cancer is one of the most common tumors globally, with a death rate of 13.7/year per 100,000 persons [1,2]
Higher expression of IGHG1 was identified in the colorectal cancer cells (HT29, SW480, SW620, and HCT116) compared to human intestinal epithelial cell (HIEC) (Figure 1b and c), suggesting that IGHG1 might be implicated in colorectal cancer progression
Considering IGHG1 was involved in the tumorigenesis of a variety of cancers, the functional role of IGHG1 in colorectal cancer was investigated in this study
Summary
Colorectal cancer is one of the most common tumors globally, with a death rate of 13.7/year per 100,000 persons [1,2]. The 5-year overall survival rate of patients with colorectal cancer at the early stage is about 90%, while approximately 30% for the patients who suffer lymph nodes or distant nodes metastases [3]. Patients with advanced colorectal cancer often face the risk of tumor metastasis, so novel strategies are required to prolong the survival rate of the patients [5]. Fluorescence-guided surgery with exogenous administration of 5-aminolevulinic acid has been used as the preoperative imaging technique for cancer detection [6]. 5-Aminolevulinic acid is metabolically converted to protoporphyrin IX (PpIX), which functions as an endogenous fluorophore and is used in fluorescence-guided surgery for the detection of colorectal cancer [7]. PpIX is complexed with Fe2+ to produce heme under the catalysis of ferrochelatase (FECH), and heme was reported to be related to the malignant
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