Background Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) was reported to be aberrantly upregulated and promote esophageal squamous cell carcinoma (ESCC) cell progression. Nevertheless, the molecular mechanism of NEAT1 involved in the competing endogenous RNA (ceRNA) regulatory network in ESCC progression remains poorly defined. Methods The expressions of NEAT1, miR-129, and C-terminal-binding protein 2 (CTBP2) in ESCC cells were examined by qRT-PCR. The effects of NEAT1 knockdown and miR-129 overexpression, or along with CTBP2 upregulation, on ESCC cell viability and invasion were explored by CCK-8 and transwell invasion assays, respectively. Luciferase reporter assay in combination with RIP was performed to confirm the interaction between NEAT1, miR-129, and CTBP2. Results NEAT1 and CTBP2 were upregulated and miR-129 was downregulated in ESCC cells. Either NEAT1 knockdown or miR-129 overexpression suppressed ESCC cell viability and invasion. Moreover, NEAT1 functioned as an endogenous sponge to downregulate miR-129 by competitively binding to miR-129, thereby leading to the derepression of CTBP2, a target of miR-129. CTBP2 restoration overturned cell viability and invasion suppression mediated by NEAT1 knockdown or miR-129 overexpression. Conclusion LncRNA NEAT1 regulated ESCC cell viability and invasion via the miR-129/CTBP2 axis, contributing to the better understanding of the molecular mechanism of ESCC pathogenesis and progression.

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Myocardial infarction (MI) is a leading cause of death worldwide for which there is no cure. Although cardiac cell death is a well-recognized pathological mechanism of MI, therapeutic blockade of cell death to treat MI is not straightforward. Death receptor 5 (DR5) and its ligand TRAIL [tumor necrosis factor (TNF)–related apoptosis-inducing ligand] are up-regulated in MI, but their roles in pathological remodeling are unknown. Here, we report that blocking TRAIL with a soluble DR5 immunoglobulin fusion protein diminished MI by preventing cardiac cell death and inflammation in rats, pigs, and monkeys. Mechanistically, TRAIL induced the death of cardiomyocytes and recruited and activated leukocytes, directly and indirectly causing cardiac injury. Transcriptome profiling revealed increased expression of inflammatory cytokines in infarcted heart tissue, which was markedly reduced by TRAIL blockade. Together, our findings indicate that TRAIL mediates MI directly by targeting cardiomyocytes and indirectly by affecting myeloid cells, supporting TRAIL blockade as a potential therapeutic strategy for treating MI.

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