Mechanism and Role of the Neuropeptide LGI1 Receptor ADAM23 in Regulating Biomarkers of Ferroptosis and Progression of Esophageal Cancer

Abstract

Background. According to recent studies, ferroptosis is closely related to the efficacy and prognosis of tumour treatment. However, the role of ferroptosis in esophageal squamous cell carcinoma (ESCC) has not been explored comprehensively. Materials and Methods. The esophageal cancer (EC) transcriptome data was downloaded from The Cancer Genome Atlas (TCGA), then analyzed, to obtain the differentially expressed messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) between groups with the low and high Ferroptosis Potential Index (FPI) and construct a ferroptosis-associated ceRNA network. In addition, the expression of ARHGEF26-AS1 and miR-372-3p in ESCC cell lines was assessed, and the appropriate cell lines were selected. The interaction between ARHGEF26-AS1, miR-372-3p, and ADAM23 was also determined through a dual-luciferase reporter assay. Moreover, the Western blot, Cell Counting Kit-8 (CCK-8), wound healing, cell viability, and cell death assays were conducted to establish the biological functions of the ARHGEF26-AS1/miR-372-3p/ADAM23 pathway in ESCCs. Results. An FPI scoring model reflecting the activity of the ferroptosis pathway was constructed, and a ferroptosis-associated ceRNA network was established. The findings revealed that low expression of ADAM23 and ARHGEF26-AS1 as well as high expression of miR-372-3p was associated with poor prognosis and a lower FPI score in EC patients. Functionally, overexpression of ADAM23 and ARHGEF26-AS1 and the miR-372-3p inhibitor not only promoted ferroptosis in ESCC cells in vitro but also inhibited the proliferation and migration of cells. Mechanistically, ARHGEF26-AS1 upregulated the expression of ADAM23 by competitively binding to miR-372-3p. Conclusions. The study showed that the lncRNA, ARHGEF26-AS1 acts as a miR-372-3p sponge that regulates the neuropeptide LGI1 receptor ADAM23 expression. This in turn not only inhibits the proliferation and migration of ESCC cells but also upregulates the ferroptosis pathway. A neuropeptide-related ferroptosis regulatory pathway was identified in this study.

Prognostic microRNAs associated with phosphoserine aminotransferase 1 in gastric cancer as markers of bone metastasis

“…MicroRNAs (miRNAs) belong to a family of non-coding RNAs of 20-24 nucleotides in length. MiRNAs are significantly associated with tumor development and metastasis (Liu et al, 2019;Wang et al, 2019;Chen et al, 2021;Zhang and Liu, 2021;Cao et al, 2022). Compared with normal tissues, miRNA expression is down-regulated in various cancers.…”

Posttreatment Recurrence and Death Patterns in Patients with Advanced Esophageal Cancer

“…Many biomarkers for EC have been reported [ 5 – 7 ]. However, some studies reported lymph node metastases patterns at the time of surgery [ 8 , 9 ], and to attribute the recurrence/metastasis patterns and death patterns of advanced EC to patients' clinical characteristics is still a big challenge.…”

miR-17-5p/HOXA7 Is a Potential Driver for Brain Metastasis of Lung Adenocarcinoma Related to Ferroptosis Revealed by Bioinformatic Analysis

“…In the TCGA nM-LUAD dataset, we used the GSVA package to calculate the enrichment scores of ferroptosis-related gene sets (including ACSL4, ALOX15, COQ10A, COQ10B, FDFT1, GPX4, HMGCR, SLC3A2, SLC7A11, NFE2L2, NOX1, NOX3, NOX4, and NOX5 ). This followed the ferroptosis index (FPI) calculation by applying the standardized method as described previously ( 40 , 41 ). These FPI scores are used to quantify the likelihood of ferroptosis of cells within a tumor or tissue and based on median FPI scores, nM-LUAD patients are divided into high and low FPI groups.…”