MircroRNAs (miRNAs) are considered as essential regulators in the tumorigenesis and chemoresistance of multiple cancer types. In the present study, it was demonstrated that the expression levels of miR-125b were significantly downregulated in the tissues of patients with breast cancer (BC), as well as the BC cell lines in vitro. To study the association between chemoresistance and miR-125b in BC, doxorubicin (DOX)-resistant MCF-7 (MCF-7/R) cells were established, and gain- and loss-of-function experiments were performed. It was demonstrated that the overexpression of miR-125b increased the sensitivity of MCF-7/R cells to DOX. Furthermore, it was revealed that the sensitization of miR-125b mimics to DOX-induced cell death was regulated by the hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) vector and HAX-1 small interfering RNA. These results emphasized the notable function of miR-125b and its target of HAX-1 in regulating DOX-resistance. In addition, it was demonstrated that the miR-125b mimics promoted the loss of the mitochondrial membrane potential and the generation of reactive oxygen species induced by DOX treatment in MCF-7/R cells. These data suggest that the miR-125b-HAX-1-mitochondria pathway has a notable function in the treatment of DOX-resistant BC cells, which may provide a novel target for the chemotherapy of BC.

Background. It has been shown that low-density lipoprotein receptor-related protein 1B (LRP1B) mutations correlate with tumor mutation burden (TMB) and prognosis in patients with melanoma and non-small-cell lung cancer, while the relationship between LRP1B mutations and TMB in gastric cancer needs further study. This study is aimed at exploring the relationship between LRP1B mutations and TMB in gastric cancer. Methods. Mutation frequency profiles of the genes in patients with gastric cancer in TCGA-STAD dataset were analyzed by bioinformatics analysis. The relationship among LRP1B mutations, TMB, and patient clinical features in gastric cancer was investigated by the chi-square test. The TMB prediction capacity based on LRP1B mutation status was evaluated by ROC curves. Results. LRP1B is one of the top 10 genes with high gene mutation frequency in gastric cancer. The mutation status of LRP1B in gastric cancer patients was significantly correlated with age and TP53 and MUC16 mutation status. The result of ROC curve analysis revealed that the mutation status of LRP1B could be considered as an indicator of the degree of TMB in patients with gastric cancer. Conclusion. This study presented the relationship between TMB and LRP1B mutations in gastric cancer, providing a novel perspective for gastric cancer prognosis and therapy.

Background Primary duodenal cancer (PDC) is rare, especially signet-ring cell carcinoma (SRCC) of the duodenal bulb, and it is commonly misdiagnosed as an ulceration. Here, we report a rare case of SRCC of the duodenal bulb presenting with gastrointestinal hemorrhage in an 82-year-old man. Case presentation An 82-year-old man was admitted for gastrointestinal hemorrhage. Physical examination revealed upper abdominal tenderness and pale appearance, but was otherwise unrevealing. Laboratory workup was significant for anemia. Imaging showed no abnormalities. Two endoscopic evaluations along with interventional embolization were attempted and, unfortunately, adequate hemostasis was not achieved, resulting in distal subtotal gastrectomy, including the duodenal bulb. SRCC of the duodenal bulb was diagnosed based on pathology after surgery. Post-operatively, the patient experienced persistent gastrointestinal bleeding. Family declined further intervention and the patient eventually died one month post-resection. Conclusions SRCC in the duodenal bulb is difficult to diagnose. For those with high-risk factors, endoscopic examination and biopsy are recommended. For patients who can receive radical tumor resection, pancreaticoduodenectomy (PD) is considered a first-line option. Early diagnosis and resection have been shown to improve prognosis.