Long noncoding RNA AFAP1-AS1 acts as a competing endogenous RNA of miR-423-5p to facilitate nasopharyngeal carcinoma metastasis through regulating the Rho/Rac pathway

Background: Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long noncoding RNA, is significantly highly expressed and associated with metastasis and poor prognosis in many cancers, including nasopharyngeal carcinoma (NPC). In this study, we aim to identify the role of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC metastasis. Methods: The role of AFAP1-AS1, miR-423-5p, and FOSL2 in NPC metastasis was investigated in vitro and in vivo. Bioinformatics analysis and luciferase activity assays were used to identify the interaction between AFAP1-AS1, miR-423- 5p, and FOSL2. Additionally, real-time PCR and western blotting were used to assess the function of AFAP1-AS1 acting as an oncogenic lncRNA to promote NPC progression by regulating miR-423-5p and the downstream Rho/Rac pathway. Results: In this study, we determined that AFAP1-AS1 functions as a competing endogenous RNA in NPC to regulate the Rho/Rac pathway through miR-423-5p. These interactions can mediate the expression of RAB11B, LASP1, and FOSL2 and accelerate cell migration and invasion via the Rho/Rac signaling pathway or FOSL2. AFAP1-AS1 and FOSL2 could competitively bind with miR-423-5p to regulate several molecules, including RAB11B and LASP1 of the Rho/Rac signaling pathway. AFAP1-AS1 can also regulate the expression of LASP1, which was transcriptionally regulated by FOSL2, resulting in increased migration and invasion of NPC cells via the Rho/Rac signaling pathway. Conclusions: The observations in this study identify an important role for AFAP1-AS1 as a competing endogenous RNA (ceRNA) in NPC pathogenesis and indicate that it may serve as a potential target for cancer diagnosis and treatment

FGF10 Protects Against Renal Ischemia/Reperfusion Injury by Regulating Autophagy and Inflammatory Signaling

Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated. Herein, we report that FGF10 treatment improved renal function and histological integrity in a rat model of renal I/R injury. We observed that FGF10 efficiently reduced I/R-induced elevation in blood urea nitrogen, serum creatinine as well as apoptosis induction of RTCs. Interestingly, autophagy activation following I/R was suppressed by FGF10 treatment based on the immunohistochemistry staining and immunoblot analyses of LC3, Beclin-1 and SQSTM1/p62. Moreover, combined treatment of FGF10 with Rapamycin partially reversed the renoprotective effect of FGF10 suggesting the involvement of mTOR pathway in the process. Interestingly, FGF10 also inhibited the release of HMGB1 from the nucleus to the extracellular domain and regulated the expression of inflammatory cytokines such as TNF-α, IL-1β and IL-6. Together, these results indicate that FGF10 could alleviate kidney I/R injury by suppressing excessive autophagy and inhibiting inflammatory response and may therefore have the potential to be used for the prevention and perhaps treatment of I/R-associated AKI

MiR-200c is a cMyc-activated miRNA that Promotes Nasopharyngeal Carcinoma by Downregulating PTEN

The c-Myc transcription factor regulates a complex transcriptional program that leads to cellular transformation by targeting a large number of protein-encoding genes and non-coding RNAs. In this study, we show that a microRNA, miR-200c, is a novel c-Myc target that promotes cellular transformation and metastasis in nasopharyngeal carcinoma. MiR-200c achieves this oncogenic effect, at least in part, by targeting and inhibiting the tumor suppressor gene PTEN (phosphatase and tensin homolog), which is a key inhibitor of the AKT kinase signaling that promotes tumorigenesis in nasopharyngeal carcinoma. Our study thus identifies cMyc-miR-200c-PTEN-AKT as a functional module that promotes cellular transformation in nasopharyngeal carcinoma