Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis

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.