BackgroundAs a type of recently discovered noncoding RNA, circular RNAs (circRNAs) exert pivot biological functions in diverse cancers. However, the role of circRNA_102171 in papillary thyroid cancer (PTC) has not been investigated. Our study was focused on the functional investigation toward circRNA_102171 in PTC progression. And we also aimed to reveal its potential molecular mechanism.MethodsThe expression pattern of circRNA_102171 was determined using quantitative polymerase chain reaction (qPCR) in PTC samples and cell lines. Cell proliferation was examined utilizing CCK8, colony formation and EdU incorporation assays. Apoptosis was analyzed by Annexin V/PI staining and FACS detection. Cell migration and invasion was measured using Transwell assay. Tumor growth in vivo was determined through a xenograft assay. RNA-pulldown, RNA-IP (RIP) and RNA-EMSA were used to analyze the interaction between circRNA_102171 and CTNNBIP1.ResultsCircRNA_102171 expression was upregulated in tumor tissues and cell lines. CircRNA_102171 silencing suppressed PTC cell proliferation, migration and invasion while promoting apoptosis. CircRNA_102171 knockdown inhibited PTC growth in vivo. CircRNA_102171 interacted with CTNNBIP1 to block its interaction with the β-catenin/TCF3/TCF4/LEF1 complex, leading to activation of Wnt/β-catenin pathway.ConclusionsCircRNA_102171 overexpression promotes PTC progression through activating Wnt/β-catenin pathway in a CTNNBIP1-dependent way.
The incidence of papillary thyroid cancer (PTC) has been rapidly increasing in recent years. PTC is prone to lymph node metastasization, which further increases the recurrence rate and mortality of thyroid cancer. However, the underlying mechanisms of this process remain elusive. Several reports have shown that the microRNA miR-215 plays an important role in cancer metastasis. Here, we investigated, for the first time, the potential association between miR-215 and metastasis in PTC. The results of qPCR analysis demonstrated that miR-215 was downregulated in PTC cell lines and tissues, and lower levels of miR-215 correlated with lymph node metastasis of PTC. In vitro and in vivo assays revealed that restoration of miR-215 dramatically inhibited PTC cell proliferation and metastasis. We identified ADP ribosylation factor guanine nucleotide-exchange factor 1 (ARFGEF1) as the target, which mediated the function of miR-215. The expression of ARFGEF1 was inhibited by miR-215, and the effects of miR-215 were abrogated by re-expression of ARFGEF1. Moreover, we found that miR-215 suppressed PTC metastasis by modulating the epithelial–mesenchymal transition via the AKT/GSK-3β/Snail signaling. In summary, our study proves that miR-215 inhibits PTC proliferation and metastasis by targeting ARFGEF1 and indicates miR-215 as a biomarker for PTC prognosis.
Stroke is associated with high morbidity and mortality, and much remains unknown about the injury-related mechanisms that occur following reperfusion. This study aimed to explore the roles of Toll-like receptor 2 (TLR2) and sphingosine kinase 1 (Sphk1) in microglial cells in inflammatory responses induced by cerebral ischemia/reperfusion (I/R). For this purpose, C57BL/6 mice were randomly divided into 4 groups as follows: the sham-operated group, the I/R group, the I/R group treated with TLR2 antibody, and the I/R group treated with N,N-dimethylsphingosine. Focal cerebral I/R was induced by middle cerebral artery occlusion. Double-labeling immunofluorescence was used to observe the protein expression of TLR2 and Sphk1 in the ischemic brain tissue. Quantitative polymerase chain reaction was performed to determine the mRNA levels of TLR2 and Sphkl in ischemic brain tissue. Enzyme-linked immunosorbent assay was carried out to detect the protein contents of interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), IL-17 and IL-23 in ischemic brain tissue. The results revealed that I/R upregulated TLR2 and Sphk1 expression in microglial cells, and the inhibition of either TLR2 or Sphk1 inhibited the expression of the pro-inflammatory cytokines, IL-1β, TNF-α, IL-17 and IL-23. Notably, the inhibition of TLR2 activity also decreased Sphk1 expression. These results thus indicate that the activation of microglial cells, via a TLR2→Sphk1→pro-inflammatory cytokine (IL-1β, TNF-α, IL-17 and IL-23) pathway, may participate in I/R injury.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.