AIM2 Promotes Gastric Cancer Cell Proliferation via the MAPK Signaling Pathway

Abstract

Background. Gastric cancer (GC) is a highly prevalent tumor type. The dysregulated expression of melanoma deficiency factor 2 (AIM2) has been observed in a range of tumor types. Herein, we explore the role of AIM2 in the regulation of GC progression. Methods. Gastric cancer cells BGC-823 and MGC-803 in logarithmic growth phase were divided into blank group (control), Control group (NC) and SH-AIM2 group, respectively. Control group and SH-AIM2 group were transfected with AIM2 NC and SH-AIM2, respectively. Nude mice were divided into blank group (control) and SH-AIM2 group, and the treatment methods were the same as above. Differential AIM2 expression in GC tissues was assessed via bioinformatics analyses, after which western blotting was used for analyzing the AIM2 levels in tumor and paracancerous tissues from five stomach cancer patients. In addition, qPCR and protein imprinting were used to assess AIM2 expression levels in GC cells, and AIM2 knockdown was conducted in MGC-803 and BGC-823cells, after which colony formation and EdU incorporation assay were utilized to assess cell proliferation. The oncogenic role of AIM2 was then assessed in mice and validated through immunohistochemical analyses. Results. GC tissues and cell lines exhibited marked AIM2 overexpression. AIM2 knockdown significantly impaired GC cell proliferation and migration, as confirmed through in vitro assays. In vivo experiments showed that both the increment ability and invasion and migration ability of AIM2 knockdown group were significantly lower than that of control and NC the change of AIM2 protein level would affect the change of MAPK pathway related protein level. Conclusions. AIM2 knockdown markedly suppresses the proliferation, migration, as well as invasion of GC cells via the inhibition of MAPK signaling, thereby slowing tumor progression. Overall, these results suggest that further analyses of AIM2 may offer clinically valuable insights that can aid in the treatment of human GC.

AIM2 and Psoriasis

“…Man and his colleagues found that AIM2deficient mice presented uncontrolled proliferation of intestinal stem cells through an abnormal wingless (Wnt) signaling pathway, while inflammasome function was found to be undisrupted by assessing IL-1b, IL-18, and caspase-1 (155). Feng et al reported that AIM2 might promote cell proliferation in gastric cancer via the mitogen-activated protein kinase (MAPK) pathway (167), leading us to suspect that AIM2 might also control keratinocyte proliferation by augmenting the Wnt or MAPK pathways. Indeed, Wnt5a increases keratinocyte proliferation by secreting TNF-a, IL-12, and IL-23 but repressing the Notch1 pathways which could activate the AIM2 inflammasome (168,169).…”

“…Feng et al. reported that AIM2 might promote cell proliferation in gastric cancer via the mitogen-activated protein kinase (MAPK) pathway ( 167 ), leading us to suspect that AIM2 might also control keratinocyte proliferation by augmenting the Wnt or MAPK pathways. Indeed, Wnt5a increases keratinocyte proliferation by secreting TNF-α, IL-12, and IL-23 but repressing the Notch1 pathways which could activate the AIM2 inflammasome ( 168 , 169 ).…”

Retracted: AIM2 Promotes Gastric Cancer Cell Proliferation via the MAPK Signaling Pathway

“…Tis article has been retracted by Hindawi following an investigation undertaken by the publisher [1]. Tis investigation has uncovered evidence of one or more of the following indicators of systematic manipulation of the publication process:…”

Increased copy number of imprinted genes in the chromosomal region 20q11-q13.32 is associated with resistance to antitumor agents in cancer cell lines

“…In tumors, imprinted genes undergo multiple genomic and epigenomic alterations including single nucleotide changes, copy number changes, and changes in their DNA methylation and expression [1,2,[13][14][15][16][17][18][19][20][21]. Transcriptional upregulation, silencing, and posttranscriptional regulation of imprinted genes have been reported in different cancer categories [2,20,[22][23][24][25][26]. Some of the epigenetic changes affecting imprinted loci in tumors involve loss or gain of imprinting or an epigenetic switch of allelic expression [13,14,19,24,[27][28][29].…”

“…In cancer, epigenetic dysregulation and genomic changes in protein-coding imprinted loci and in imprinted loci encoding noncoding RNAs modulate tumor cell signaling, differentiation, metabolism, migration, apoptosis, and hormonal regulation and promote tumor growth and cell proliferation [2,8,25,30,31]. There is also growing evidence that epigenomic and genomic changes affecting some imprinted loci in tumors may affect response to cancer treatment.…”