RESUMO
BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a cancerous tumor with an extremely poor 5-year survival rate. The exploration of biomarkers for the diagnosis and treatment of PAAD is crucial in clinical practice. Krüppel-like factors (KLFs) are involved in a variety of biological functions in cells. According to multiple studies, KLF16 behave as an oncogene in prostate, breast and gastric cancers. However, no research has been done on the significance of KLF16 in PAAD. AIM: To explore the molecular mechanisms of KLF16 in PAAD. METHODS: KLF16 was identified in the tumor specimens and normal tissues by GEPIA database and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of KLF16, combined with in vitro and in vivo assays, was performed to show the functional significance of KLF16. The molecular mechanism of KLF16 was demonstrated by qRT-PCR, western blotting, immunoprecipitation assay and flow cytometry. RESULTS: We showed that KLF16 was highly expressed in PAAD patients based on the GEPIA database. KLF16 silencing suppressed while KLF16 overexpression promoted the malignant function of PAAD cells. Based on RNA sequencing, we discovered that KLF16 potentiated the expression of SMAD6 in PAAD cells. SMAD6 transcript abundance was increased and positively correlated with KLF16 expression in PAAD samples. In addition, inhibiting SMAD6 was able to mitigate the effects of KLF16 overexpression on PAAD cell processes, suggesting the importance of SMAD6 in the development of KLF16-triggered PAAD. CONCLUSION: KLF16/SMAD6 axis might be explored as a therapeutic target for PAAD therapy.
RESUMO
OBJECTIVE: To evaluate the efficacy of metformin versus a placebo in the treatment of patients with simple obesity without obesity related diseases. METHODS: A search was done on Pub-Med, EMBASE, Cochrane, and Science Citation Index Expanded databases. The main inclusion criteria included the following:(1) randomized controlled trials. (2) patients diagnosed as being overweight or obese. (3) patients were randomly assigned to receive metformin or control. Exclusion criteria included the following: patients diagnosed with an obesity related disease, such as diabetes mellitus (DM) or polycystic ovary syndrome (PCOS). RESULTS: Compared with the placebo, weighted mean difference (WMD) was 2.33 (95% CI 0.31, 4.35) kg higher with metformin (p = 0.02). Compared with the placebo, WMD was 0.57 (95% CI 0.35, 0.79) kg/m² higher with metformin(p < 0.00001). There was no significant difference in the reduction of waist circumference between the metformin group and the control group (p = 0.05). The fasting blood glucose levels were significantly lower in the metformin group than in the control group (p < 0.00001). However, no hypoglycemia was noted in the metformin group or the control group. CONCLUSION: Metformin is effective in reducing body weight of simple obesity patients, and metformin does not induce hypoglycemia as a side effect.
