PC-3-Derived Exosomes Inhibit Osteoclast Differentiation by Downregulating miR-214 and Blocking NF-κB Signaling Pathway

Abstract

Prostate cancer is a serious disease that can invade bone tissues. These bone metastases can greatly decrease a patient’s quality of life, pose a financial burden, and even result in death. In recent years, tumor cell-secreted microvesicles have been identified and proposed to be a key factor in cell interaction. However, the impact of cancer-derived exosomes on bone cells remains unclear. Herein, we isolated exosomes from prostate cancer cell line PC-3 and investigated their effects on human osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. The potential mechanism was evaluated by qRT-PCR, western blotting, and microRNA transfection experiments. The results showed that PC-3-derived exosomes dramatically inhibited osteoclast differentiation. Marker genes of mature osteoclasts, including CTSK, NFATc1, ACP5, and miR-214, were all downregulated in the presence of PC-3 exosomes. Furthermore, transfection experiments showed that miR-214 downregulation severely impaired osteoclast differentiation, whereas overexpression of miR-214 promoted differentiation. Furthermore, we demonstrated that PC-3-derived exosomes block the NF-κB signaling pathway. Our study suggested that PC-3-derived exosomes inhibit osteoclast differentiation by downregulating miR-214 and blocking the NF-κB signaling pathway. Therefore, elevating miR-214 levels in the bone metastatic site may attenuate the invasion of prostate cancer.

Zhen-Wu-Tang Protects IgA Nephropathy in Rats by Regulating Exosomes to Inhibit NF-κB/NLRP3 Pathway

“…NF-κB expression is negatively correlated with the prognosis of IgAN patients ( Silva et al., 2011 ). Besides, there is growing evidence that exosomes can mitigate various inflammatory responses by inhibiting the NF-κB signaling pathway ( Duan et al., 2019 ; Wang Z. et al., 2019 ). However, it is rarely reported in IgAN.…”

MicroRNA‑214 promotes the EMT process in melanoma by downregulating CADM1 expression

“…These results were similar to those of previous studies ( 46 – 48 ), thus indicating that miR-214 increased the invasion and migration of melanoma by downregulating CADM1 to promote the EMT process. However, it has also been revealed that miR-214 promotes cancer progression by activating the NF-κB signaling pathway ( 49 ). Therefore, future studies should focus on the association between melanoma and the NF-κB signaling pathway.…”

Globally learning gene regulatory networks based on hidden atomic regulators from transcriptomic big data

“…Considering that resampling can relieve sample bias in machine learning, especially when sample size is small or moderate [57], we also devise a resampling procedure for more reliable inference: 1) Randomly selecting a subset of s samples from the total samples without replacement and running dlGRN with the s samples; 2) Repeating 1) N times to obtain N cs by [4] for each pair of regulators and target genes; 3) Averaging the resulting N cs as final results. Specifically, we set s = 25% × n and N = 2 × n as default.…”

“…Gene regulatory networks (GRNs) play fundamental and central roles in response to endogenous or exogenous stimuli for maintaining the viability and plasticity of cells [1,2]. Although it has been acknowledged that aberrant gene networks can be a key driver of human diseases including cancer, little is known about the GRNs of cancer, which has largely impeded the development of cancer precision medicine [3][4][5]. In these years, a deluge of omics big data has been generated and accumulated worldwide, which provides an unprecedented opportunity for reverse engineering GRNs in a cost-efficient way [6,7].…”