Vital osteocytes have been well known to function as an important orchestrator in the preservation of robustness and fidelity of the bone remodeling process. Nevertheless, some key pathological factors, such as sex steroid deficiency and excess glucocorticoids, and so on, are implicated in inducing a bulk of apoptotic osteocytes, subsequently resulting in resorption-related bone loss. As much, osteocyte apoptosis, under homeostatic conditions, is in an optimal state of balance tightly controlled by pro- and anti-apoptotic mechanism pathways. Importantly, there exist many essential signaling proteins in the process of osteocyte apoptosis, which has a crucial role in maintaining a homeostatic environment. While increasing in vitro and in vivo studies have established, in part, key signaling pathways and cross-talk mechanism on osteocyte apoptosis, intrinsic and complex mechanism underlying osteocyte apoptosis occurs in various states of pathologies remains ill-defined. In this review, we discuss not only essential pro- and anti-apoptotic signaling pathways and key biomarkers involved in these key mechanisms under different pathological agents, but also the pivotal role of apoptotic osteocytes in osteoclastogenesis-triggered bone loss, hopefully shedding new light on the attractive and proper actions of pharmacotherapeutics of targeting apoptosis and ensuing resorption-related bone diseases such as osteoporosis and fragility fractures.

MicroRNAs are a class of non-coding RNAs that function as key regulators of gene expression at the post-transcriptional level. In our previous research, we found that miR-23a was significantly up-regulated in human gastric adenocarcinoma cells. In the current study, we demonstrate that miR-23a suppresses paclitaxel-induced apoptosis and promotes the cell proliferation and colony formation ability of gastric adenocarcinoma cells. We have identified tumor suppressor interferon regulator factor 1 (IRF1) as a direct target gene of miR-23a. We performed a fluorescent reporter assay to confirm that miR-23a bound to the IRF1 mRNA 3′UTR directly and specifically. The ectopic expression of IRF1 markedly promoted paclitaxel-induced apoptosis and inhibited cell viability and colony formation ability, whereas the knockdown of IRF1 had the opposite effects. The restoration of IRF1 expression counteracted the effects of miR-23a on the paclitaxel-induced apoptosis and cell proliferation of gastric adenocarcinoma cells. Quantitative real-time PCR showed that miR-23a is frequently up-regulated in gastric adenocarcinoma tissues, whereas IRF1 is down-regulated in cancer tissues. Altogether, these results indicate that miR-23a suppresses paclitaxel-induced apoptosis and promotes cell viability and the colony formation ability of gastric adenocarcinoma cells by targeting IRF1 at the post-transcriptional level.

No abstract

MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression. It has been reported that miRNAs are involved in host-virus interaction, but evidence that cellular miRNAs promote virus replication has been limited. Here, we found that miR-23a promoted the replication of human herpes simplex virus type 1 (HSV-1) in HeLa cells, as demonstrated by a plaque-formation assay and quantitative real-time PCR. Furthermore, interferon regulatory factor 1 (IRF1), an innate antiviral molecule, is targeted by miR-23a to facilitate viral replication. MiR-23a binds to the 3′UTR of IRF1 and down-regulates its expression. Suppression of IRF1 expression reduced RSAD2 gene expression, augmenting HSV-1 replication. Ectopic expression of IRF1 abrogated the promotion of HSV-1 replication induced by miR-23a. Notably, IRF1 contributes to innate antiviral immunity by binding to IRF-response elements to regulate the expression of interferon-stimulated genes (ISGs) and apoptosis, revealing a complex interaction between miR-23a and HSV-1. MiR-23a thus contributes to HSV-1 replication through the regulation of the IRF1-mediated antiviral signal pathway, which suggests that miR-23a may represent a promising target for antiviral treatments.