hsa-mir-133a-2 promotes the proliferation and invasion of cervical cancer cells by targeting the LAMB3-mediated PI3K/ATK pathway.

OBJECTIVE: Cervical cancer, one of the common types of malignant tumors progressed in women, is on the rise in developing countries. Numerous previous studies have demonstrated that hsa-mir-133a-2 miRNA is abnormally expressed in cervical cancer cells. However, its fundamental mechanism in cervical cancer needs to be further clarified. Our study set out to investigate the effect of hsa-mir-133a-2 on the phenotypes of cervical cancer cells as well as any potential molecular processes involved in the proliferation and invasion of cervical cancer cells. METHODS: The Cancer Genome Atlas-cervical squamous cell carcinoma and endocervical adenocarcinoma(TCGA-CESC) was adopted in order to verify the expression of hsa-mir-133a-2 in cervical cancer tissues and to identify its potential targets. The interaction between Laminin subunit beta-3(LAMB3) and hsa-mir-133a-2 was verified by TargetScan database as well as Luciferase reporter assay. The Cell Counting Kit-8 (CCK8) and transwell methods were utilized to assess the influence of hsa-mir-133a-2 on the proliferation and invasion characteristics of cervical cancer cells. We studied the role that hsa-mir-133a-2 plays in cervical cancer progression through Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis as well as Western Blot (WB) experiment. RESULTS: Down-regulation of hsa-mir-133a-2 was detected in cervical cancer tissues. It directly targeted LAMB3 and negatively regulated LAMB3 expression. The overexpression of hsa-mir-133a-2 has a significant inhibiting effect on cervical cancer cell proliferation and invasion. The overexpression of hsa-mir-133a-2 significantly inhibits the proliferation and invasion of cervical cancer cells. Moreover, the LAMB3 was able to up-regulate the phosphorylation levels of AKT and phosphatidylinositol 3-kinase (PI3K) protein in cervical cancer cells. hsa-mir-133a-2 could also modulate the PI3K/AKT signaling pathway by targeting LAMB3. CONCLUSION: hsa-mir-133a-2 inhibits cervical cancer cell proliferation and invasion by indirectly regulating the PI3K/AKT signaling pathway, providing us with a new clinical treatment strategy for cervical cancer.

Advanced glycation end products correlate with breast cancer metastasis by activating RAGE/TLR4 signaling.

INTRODUCTION: This study was aimed to investigate the mechanisms of advanced glycation end products (AGEs) in promoting invasion and metastasis of breast cancer. RESEARCH DESIGN AND METHODS: Patients with 131 breast cancer were enrolled in a cohort and followed up to investigate the association between AGEs and metastasis. Serum AGE concentrations were detected by ELISA. Breast cancer MDA-MB-231 cells were exposed to generated AGE-bovine serum albumin (BSA). CCK-8 assay was used to select the non-cytotoxic concentrations of AGE-BSA. Small interfering RNA was used to knock down Toll-like receptor 4 (TLR4). Migration and invasion were evaluated by wound healing and transwell assays. Real-time PCR and western blotting were used to detect the gene expressions. RESULTS: In the cohort study, metastasis incidence was significantly correlated with serum AGE concentrations in patients with breast cancer (adjusted OR=1.75, 95% CI=1.20 to 2.57, p=0.004). During follow-up, metastasis interval was significantly shorter in diabetic than non-diabetic subjects. In the in vitro study, AGE-BSA incubation significantly promoted migration and invasion of cancer cells in a concentration-dependent manner. AGE-BSA dramatically increased expressions of receptor for AGEs (RAGE), TLR4, myeloid differentiation factor (MyD88), matrix metalloproteinase 9 (MMP9), promoted nuclear translocation of nuclear factor κB (NFκB) p65, but decreased the expression of inhibitor of NFκB (IκBα). TLR4 silencing significantly suppressed migration and invasion of cancer cells exposed to AGE-BSA. TLR4 silencing reduced the expression of MyD88 and MMP9, as well as nuclear translocation of NFκB p65 but increased IκBα expression in AGE-BSA-incubated breast cancer cells. CONCLUSIONS: AGEs are correlated with metastasis of breast cancer. AGEs' promoting effects on migration and invasion of breast cancer cells via activating RAGE/TLR4/MyD88 signaling were suggested as the involved mechanism.

Clinical analysis of chronic active EBV infection with coronary artery dilatation and a matched case-control study.

OBJECTIVE: To investigate the clinical characteristics, treatment, prognosis and risk factors for chronic active Epstein-Barr Virus infection (CAEBV) associated with coronary artery dilatation (CAD) in children. METHODS: Children with CAEBV associated with CAD hospitalized at Beijing Children's Hospital, Capital Medical University from March 2016 to December 2019 were analyzed. Children with CAEBV without CAD were selected as the control group and matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis of the children were collected in both groups. RESULTS: There were 10 children with CAEBV combined with CAD, including 6 males and 4 females, accounting for 8.9% (10/112) of CAEBV patients in the same period, with an onset age of 6.05 (2.8-14.3) years. The median follow-up time was 20 (6-48) months. All the patients had high copies of EBV-DNA in whole blood [1.18 × 107 (1.90 × 105-3.96 × 107) copies/mL] and plasma [1.81 × 104 (1.54 × 103-1.76 × 106) copies/mL], and all biopsy samples (bone marrow, lymph nodes or liver) were all positive for Epstein-Barr virus-encoded small RNA. Among the 10 children, 8 had bilateral CAD, and 2 patients had unilateral CAD. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). The others were waiting for HSCT. At the time of the last patients follow up record, the CAD had returned to normal in 3 patients, and the time from the diagnosis of CAD to recovery was 21 (18-68) days. LDH, serum ferritin, TNF-α and IL-10 levels were statistically significantly different between the two groups (P = 0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P = 0.416). CONCLUSION: The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients who had high LDH, serum ferritin, TNF-α, and IL-10 levels early in their illness were more likely to develop CAD.

Clinical Analysis of Pediatric Systemic Juvenile Xanthogranulomas: A Retrospective Single-Center Study.

Objective: To investigate the clinical characteristics, treatment, and prognosis of children with systemic juvenile xanthogranuloma (JXG). Methods: Clinical data of children with JXG who were hospitalized in Beijing Children's Hospital, Capital Medical University, from January 2012 to December 2019 were retrospectively analyzed, including clinical manifestations, laboratory determinations, treatment, and prognosis of the children. Patients were treated with vindesine + prednisone as the first-line treatment and cytarabine + vindesine + dexamethasone ± cladribine as the second-line treatment. Results: Ten patients, including 8 males and 2 females, with a median of onset age of 1.95 (0.80-7.30) years, exhibited multi-system dysfunction. The median age of diagnosis was 2.45 (1.30-12.10) years. The most common location of extracutaneous lesions was the central nervous system (6 cases), followed by the lung (5 cases) and bone (4 cases). Nine patients underwent first-line chemotherapy, and 6 patients underwent second-line chemotherapy, including 5 patients with poorly controlled disease after first-line treatment. The median observation time was 29 (3-115) months. Nine patients survived, whereas one patient died of respiratory failure caused by pulmonary infection. At the end of follow-up, 7 patients were in active disease (AD)/regression state (AD-better), and 2 patients were in an AD/stable state (AD-stable). Three patients had permanent sequelae, mainly central diabetes insipidus. The rates of response to the first-line treatment and the second-line treatment were 40.0 and 66.7% respectively. Conclusion: The chemotherapy protocol for Langerhans cell histiocytosis (LCH) may be effective for patients with systemic JXG. Central nervous system involvement may not impact overall survival, but serious permanent sequelae may occur.