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Background/aims: MicroRNAs (miRNAs) are non-coding small RNAs that regulate cell proliferation and functions by interfering with the translation of target mRNAs. Altered expression of miRNA is known to induce various human malignancies, but little is known about the role of miRNAs in esophageal squamous cell carcinoma (ESCC)., Methods: RT-PCR and Western blot were used to examine the expression of miRNAs and candidate genes in 40 pairs of squamous cell carcinoma of human. MiR-16 mimics and inhibitor were transfected in human TE-1 and Eca-109 cells before detecting the cell migration, proliferation, apoptosis and cell cycle. The regulation mechanism was confirmed by luciferase reporter assay. Caspase-3 and 9 were detected by RT-PCR and Western blot., Results: Aberrant increased level of miR-16 was detected in the ESCC tissues compared with the corresponding adjacent tumor tissues. MiR-16 could inhibit cell apoptosis while promote cell proliferation by down-regulating RECK and SOX6 in TE-1 and Eca-109 cell lines through binding the 3'UTR of both RECK and SOX6 mRNA., Conclusions: Aberrant expression level of miR-16 could suppress cell apoptosis while promote growth by regulating RECK and SOX6 which play important roles in the pathogenesis of ESCC., (© 2014 S. Karger AG, Basel.)

Abstract: Glial cell line-derived neurotrophic factor (GDNF) is a potent protective factor for dopaminergic (DA) neurons, but the signaling mechanisms underlying the effect of GDNF on these neurons remain obscure. Here, both our in vivo and in vitro studies demonstrate that the majority of DA neurons express the NF-κB-inducing kinase (NIK), which is the essential kinase for mediating activation of the new alternative NF-κB signaling pathway. Additionally, we also show that GDNF induced the time/dose-dependent phosphorylation of IκB kinase α (IKKα) and p100, facilitated the processing of p100 to p52 and accelerated the translocation of NF-κB dimmers into the nuclei of DA neurons. We furtherly found that the dimmer which translocate into the nucleus was RelA/p52 not RelB/p52. Meanwhile, the attenuation of 6-OHDA-induced DA neuronal apoptosis due to GDNF was reversed subsequent to the inhibition of p100 expression by RNAi while the neuroprotective effect of GDNF on injured DA neurons was strengthened by the overexpression of p100. Our data, therefore, indicate that a new alternative NF-κB signaling pathway, which was not the classic pathway but different from the non-canonical pathway, exists in DA neurons and mediates the neuroprotective effect of GDNF on these neurons. [Copyright &y& Elsevier]