Regulation of MicroRNA-378 expression in mature human adipose tissue cells by adiponectin, free fatty acids and dexamethasone

Purpose: To investigate the effects of adiponectin (ADPN), free fatty acids (FFAs), growth hormone (GH), and dexamethasone (DEX) on miR-378 expression in human adipose tissue cells, and their influence on regulation of obesity and insensitivity to insulin.Methods: Human pre-adipocytes were cultured and differentiated. Adipocytes were treated with ADPN, FFAs, GH and DEX. RNA was isolated and quantified by real-time polymerase chain reaction (RTPCR).Results: Stimulation with FFA led to significant up-regulation of the expression of MiR-378(approximately 3.8-fold) relative to control at the 4th hour (p < 0.01) in human mature adipose tissue cells. The expression of MiR-378 was increased almost 1.5-fold by ADPN within 24 h, relative to untreated control (p < 0.05).Conclusion: The results of this study demonstrate that miR-378 expression is influenced by FFAs, ADPN, and DEX, the interaction of which may be involved in the pathogenesis of obesity-induced insensitivity to insulin. Thus, miR-378 is a potential biomarker for predicting the risk of complications, especially insulin resistance in obesityKeywords: MiR-378, Adipocytes, Adiponectin, Free fatty acids, Growth hormone, Dexamethasone, Obesity, Insulin resistanc

Insight into the Effects of Adipose Tissue Inflammation Factors on miR-378 Expression and the Underlying Mechanism

Background/Aims: Obesity and the related metabolic syndrome have emerged as major public health issues in modern society. miRNAs have been shown to play key roles in regulating obesity-related metabolic syndrome, and some miRNAs regulated by adiponectin were identified as novel targets for controlling adipose tissue inflammation. miR-378 is a candidate target that was shown to be involved in adipose differentiation, mitochondrial metabolism and systemic energy homeostasis. However, little is known about the regulatory mechanisms of miR-378 expression. To better understand the physiological role of miR-378 in obesity and metabolic syndrome, it is crucial that we understand the regulation of miR-378 gene expression in human adipocytes. Methods: In this study, we investigated the effects of adipokines and inflammatory cytokines on miR-378 expression using Real-time PCR and the potential regulatory mechanisms using luciferase reporter assays and electrophoretic mobility shift assay (EMSA). Results: We found that adipokines and cytokines upregulated miR-378 expression primarily through SREBP and C/EBP binding sites in the miR-378 promoter region. Conclusion: Our findings showed that adipokines induced miR-378 expression and revealed the most likely mechanism of adipokine-induced miR-378 dysregulation in human adipocytes. miRNAs have been shown to function in regulating obesity-related metabolic syndrome, and miR-378 may be a novel target for controlling adipose tissue inflammation. This study offers a theoretical basis for understanding systemic adipose tissue inflammation and may provide new strategies for clinical treatment

Bone Metastasis of Breast Cancer: Molecular Mechanisms and Therapeutic Strategies

Bone metastasis is a common complication of many types of advanced cancer, including breast cancer. Bone metastasis may cause severe pain, fractures, and hypercalcemia, rendering clinical management challenging and substantially reducing the quality of life and overall survival (OS) time of breast cancer patients. Studies have revealed that bone metastasis is related to interactions between tumor cells and the bone microenvironment, and involves complex molecular biological mechanisms, including colonization, osteolytic destruction, and an immunosuppressive bone microenvironment. Agents inhibiting bone metastasis (such as bisphosphate and denosumab) alleviate bone destruction and improve the quality of life of breast cancer patients with bone metastasis. However, the prognosis of these patients remains poor, and the specific biological mechanism of bone metastasis is incompletely understood. Additional basic and clinical studies are urgently needed, to further explore the mechanism of bone metastasis and develop new therapeutic drugs. This review presents a summary of the molecular mechanisms and therapeutic strategies of bone metastasis of breast cancer, aiming to improve the quality of life and prognosis of breast cancer patients and provide a reference for future research directions