ERO1A (Endoplasmic Reticulum Oxidoreductase 1 Alpha)

This reviews provide an in depth summary regarding ERO1α in various disease processes, including cardiovascular diseases, diabetes, and cancer. Furthermore, it highlights the potential of ERO1α as a potential biomarker and a novel therapeutic target in clinical diseases.

Knockdown of ERO1A or IDO1 blockade reversed the pro-tumor effects of TCF21 loss. In conclusion, TCF21 downregulation in LUAD activates the ERO1A-IDO1 axis, enabling immune escape from CD8+ T cell killing and accelerating malignancy.

The most potent compound, I29, featuring a mono ortho-fluorine substitution, demonstrated improved inhibitory activity (IC₅₀ = 2.6µM) and efficacy in preclinical models of TNBC and SEPN1-related myopathy. These findings highlight ERO1A's pathological role in cancer and congenital muscle disease and support its inhibition as a promising therapeutic strategy for conditions characterized by chronic ER and oxidative stress.

Furthermore, correlation with clinical data from the TCGA database revealed that m6A-associated DEGs, such as HMGA1, ERO1A, LRFN4, SNTN, SLC2A1, DNASE2B, and VSIG2, were prognostically significant in NSCLC. This study underscores the pivotal role of m6A modifications in NSCLC and highlights the potential of dRNA-seq for identifying RNA epigenetic changes that may serve as novel therapeutic targets.

This study indicated that different risk score groups exhibited different tumor mutation burden, immune microenvironment cell infiltration, immune response, differentially expressed genes, functional characteristics, correlations with immune checkpoint genes, and drug sensitivity. We established a novel ferroptosis-related oxidative stress gene-related model that possesses potential predictive value for prognosis of patients with LUAD, immunotherapy response, and chemotherapeutic drug sensitivity, and indicated its potential applicability in clinical practice.

We discuss mechanistic links, including VEGF-A maturation and PD-L1-mediated immune evasion, and highlight recent advances in small-molecule ERO1α inhibitors and preclinical therapeutic strategies. By consolidating molecular insights and translational considerations, this review underscores ERO1α as both a promising therapeutic target and potential prognostic marker, offering guidance for future drug development and targeted interventions in redox-dependent cancer pathways.

Our findings identify ERO1A + Epi as a significant driver of colorectal cancer progression. The ERO1A + Epi_TME_Score-based ETSRM provides a robust prognostic tool, offering new insights into CRC pathogenesis and highlighting potential therapeutic targets for improved patient outcomes.

This study constructed a prognostic risk model for LUAD based on 3 MAM genes, revealing a potential link between MAM genes and LUAD, offering new insights into clinical treatment and prognosis.

2',4'-DHC induces ferroptosis in CCA cells through the ERO1A/GPX4 axis and inhibits malignant progression. 2',4'-DHC drug-adjuvant therapy may enhance the efficacy of current anticancer treatments. It also holds promise as a prognostic molecular marker and therapeutic target in CCA.

Our study characterizes the metabolic heterogeneity of CRC and suggests a potential role for HGS cells in shaping the tumor microenvironment. The molecular features identified here may offer insights into metabolic dependencies that could be explored for future therapeutic targeting.

In the treatment of CC, 5-fluorouracil (5-FU) is one of the main components of chemotherapeutic combinations, but severe chemical resistance still occurs...Next, we verified that knocking down ERO1α promoted miR-451a and inhibited ARF1 expression, thus promoting ER stress and ultimately inhibiting the progression of CC. In addition, knocking down ERO1α promoted ER stress and weakened CC cell resistance to 5-FU.  Our studies revealed that ERO1α could mediate ER stress to regulate the progression of CC and 5-FU resistance through the miR-451a/ARF1 axis, which may provide new treatment directions and molecular targets for CC.

TCF21 directs its action towards ERO1A, thereby inhibiting the glycolysis-mediated promotion of immune evasion in LUAD cells. As such, the TCF21/ERO1A axis could be harnessed as a therapeutic target and a prognosis marker in LUAD.