MicroRNA-409-5p Inhibits GIST Tumorigenesis and Improves Imatinib Resistance by Targeting KDM4D Expression

Objective Gastrointestinal stromal tumors(GISTs)can rapidly proliferate through angiogenesis.Previous studies indicated the potential influence of microRNA on the progression of tumor immature angiogenesis.This study aimed to explore the specific mechanism by which microRNA-409-5p(miR-409-5p)contributes to GIST.Methods To identify genes potentially involved in the development and progression of GIST,the differences of miR-409-5p between tumors and adjacent tissues were first analyzed.Following this analysis,target genes were predicted.To further investigate the function of miRNA in GIST cells,two GIST cell lines(GIST-T1 and GIST882)were transfected with lentiviruses that stably expressed miR-409-5p and scrambled miRNA(negative control).Later,the cells were subjected to Western blotting and ELSA to determine any differences in angiogenesis-related genes.Results In GISTs,there was a decrease in the expression levels of miR-409-5p compared to the adjacent tissues.It was observed that the upregulation of miR-409-5p in GIST cell lines effectively inhibited the proteins hypoxia-inducible transcription factor 1β(HIF1β)and vascular endothelial growth factor A(VEGF-A).Further investigations revealed that miR-409-5p acted as an inhibitor of angiogenesis by binding to the 3′-UTR of Lysine-specific demethylase 4D(KDM4D)mRNA.Moreover,the combination of miR-409-5p with imatinib enhanced its inhibitory effect on angiogenesis.Conclusion This study demonstrated that the miRNA-409-5p/KDM4D/HIF1β/VEGF-A signaling pathway could serve as a novel target for the development of therapeutic strategies for the treatment of imatinib-resistance in GIST patients.

Aseptic abscess in the abdominal wall accompanied by monoclonal gammopathy simulating the local recurrence of rectal cancer:A case report

BACKGROUND Infectious abscesses in the abdominal wall can be secondary to retained foreign bodies(e.g.,stones,use of artificial mesh,use of silk yarn in surgical suture),inflammatory diseases(e.g.,acute appendicitis),and perforated malignancies of the digestive tract(particularly the colon).Aseptic abscesses(AAs)are relatively rare.To the best of our knowledge,this is the first report of an AA in the abdominal wall accompanied by monoclonal gammopathy of undetermined significance(MGUS)at 5 years after laparoscopic proctectomy.CASE SUMMARY A 72-year-old female patient presented with an enlarged painless mass in the lower abdomen for 1 year.She had a history of obesity,diabetes,and MGUS.Her surgical history was laparoscopic resection for rectal cancer 6 years prior,followed by chemotherapy.She was afebrile.Abdominal examination revealed a smooth abdomen with a clinically palpable solid mass under a laparotomy scar in the left lower quadrant.No obvious tenderness or skin redness was spotted.Laboratory data were not remarkable.Computed tomography scan revealed a low-density mass of 4.8 cm in diameter in the lower abdominal wall,which showed high uptake on positron emission tomography.The preoperative diagnosis was an abscess or tumor,and surgical resection was recommended.The mass was confirmed to be an AA by microbiological and pathological examinations.The patient recovered well after surgery.There was no evidence of recurrence 2 years later.CONCLUSION It is important to consider underlying conditions(diabetes,chemotherapy,MGUS)which may contribute to AA formation in the surgical wound.