Downregulated microRNA‐150 upregulates IRX1 to depress proliferation, migration, and invasion, but boost apoptosis of gastric cancer cells

Abstract

Objective Many studies have reported the correlation of microRNAs (miRNAs) with cancers, yet few have proposed the function of miR‐150 in gastric cancer. This study intends to discuss the role of miR‐150 in gastric cancer development by regulating IRX1. Methods Gastric cancer tissues and adjacent tissues were collected. MiR‐150‐3p, IRX1, CXCL14, and NF‐κB (p65) expressions were detected. Gastric cancer cell lines SNU‐1 and MKN‐45 were used for subsequent cellular experiments. Cell proliferation, colony formation, migration and invasion, apoptosis, and cell cycle distribution in SNU‐1 and MKN‐45 cells were determined via gain‐of and loss‐of‐function assays. The tumor growth in nude mice was also detected. Results MiR‐150, CXCL14, and NF‐κB (p65) were upregulated and IRX1 was downregulated in gastric cancer tissues and cells. CXCL14 and NF‐κB (p65) expression was positively related to miR‐150 expression and negatively to IRX1 expression. MiR‐150 inhibition and IRX1 overexpression in SNU‐1 cells restricted viability, colony formation, migration, and invasion abilities, but boosted apoptosis of gastric cancer cells in vitro, and also repressed tumor growth in vivo. These results could be reversed by miR‐150 elevation and IRX1 silencing, and the results from in vivo and in vitro experiments were consistent. Conclusion Our study reveals that miR‐150 downregulation restrains proliferation, migration, and invasion, while facilitating apoptosis of gastric cancer cells by upregulating IRX1.

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets

“…Some differentially expressed non-marker genes confirmed clustering results from another perspective. Overexpression of GKN1 in epithelial cells ( Yoon et al, 2013 ), IGLL5 in B cells ( Zheng et al, 2021 ), TPSAB1 in mast cells ( Konnikova et al, 2021 ), and RGS5 in smooth muscle cells ( Silini et al, 2012 ) are consistent with previous studies, while CXCL14 in fibroblasts ( Wu et al, 2020 ) suggests that the conclusion from bulk RNA-seq may not be precise or versatile enough. Together with marker genes, these genes constitute 64 DEGs between IM and EGC, which reflect transcriptional heterogeneity among different cell types.…”

Expression profile, prognostic values, and immune infiltration of IRX family members in lung adenocarcinoma

“…MiR-646 promotes invasive ductal carcinoma (IDC) tumorigenesis through regulation of the TET1/IRX1/HIST2H2BE axis (24). Down-regulated microRNA-150 upregulates IRX1 to inhibit proliferation, migration, and invasion, but promotes apoptosis in gastric cancer cells (25). Protein arginine methyltransferase 5-mediated epigenetic silencing of IRX1 contributes to the tumorigenicity and metastasis of gastric cancer (26).…”

Iroquois Family Genes in Gastric Carcinogenesis: A Comprehensive Review

“…In a study by Yu and colleagues [ 78 ] evaluating the relationship between loss of heterozygosity (LOH) of 5p and GC histological phenotype, a deletion region at 5p15.33 was found covering three candidate genes, including IRX1 , that was mainly related to the IGC subtype. The expression of IRX1 was reduced or lost in some GC tissues and cell lines; however, no mutations were found in the coding region of the gene [ 79 , 80 ]. Nevertheless, single nucleotide polymorphisms (SNPs) in IRX1 were identified as GC risk-associated SNPs through genome-wide association analysis of 50 GC samples and 50 normal controls [ 81 ].…”

“…BDKRB2, a downregulated gene associated with angiogenesis in IRX1 -transfected gastric cancer cells, is a downstream target gene of IRX1 and was identified as a potential target for anticancer strategies [ 85 ]. Similarly, the inhibition of a microRNA upregulated in GC cells, miR-150, which targets IRX1 sequences, restrains proliferation, migration, and invasion while facilitating apoptosis of gastric cancer cells by upregulating IRX1 and represses tumor growth in vivo [ 80 ]. Furthermore, the arginine methyltransferase 5 (PRMT5) protein was identified as a major upstream regulator of IRX1 in GC.…”