Pulmonary vascular endothelial cell (PVEC) injury following acute lung injury or acute respiratory distress syndrome seriously affects disease development. Recently, accumulating evidence has suggested that long noncoding RNA (lncRNA) exerts significant effects in vascular endothelial cell injury. However, PRNCR1, a novel lncRNA, remains scarcely understood in terms of its functions in PVEC injury. Both in vivo and in vitro models of PVEC injury were constructed by lipopolysaccharide (LPS) administration. The relative expressions of PRNCR1, miR‐330‐5p, and TLR4 were detected by quantitative reverse transcription‐polymerase chain reaction, Western blot, and immunohistochemistry. Besides, gain and loss assays of PRNCR1/miR‐330‐5p were conducted to verify their effects on LPS‐induced PVEC injury. Cell Counting Kit‐8 assay used to measure cell viability and flow cytometry was used to detect apoptosis. Besides, the protein levels of caspase 3, nuclear factor‐κB (NF‐κB), and inflammatory cytokines (including tumor necrosis factor‐α, interleukin‐1β [IL‐1β], and IL‐6) were evaluated via Western blot and enzyme‐linked immunosorbent assay. Moreover, a dual‐luciferase activity experiment and RNA immunoprecipitation were applied to confirm the targeting relationship between PRNCR1 and miR‐330‐5p, miR‐330‐5p, and TLR4. PRNCR1 and TLR4 levels were significantly upregulated in LPS‐treated PVEC, both in vivo and in vitro, while miR‐330‐5p were downregulated. Inhibiting PRNCR1 or overexpressing miR‐330‐5p markedly attenuated LPS‐induced PVEC injury, expressions of TLR4, NF‐κB, and inflammatory cytokines. Mechanistically, PRNCR1 functioned as a competitive endogenous RNA by sponging miR‐330‐5p and then promoting TLR4 expression. PRNCR1 was upregulated in LPS‐induced PVEC and aggravated its injury via modulating the miR‐330‐5p/TLR4 axis.

Activated pancreatic stellate cells (PSCs) with an increased proliferation and migration ability are the partners in crime with pancreatic cancer cells. Acid-sensing ion channel 1 (ASIC1) is expressed in pancreatic cancer and PSCs, and especially, it mediates the activation of PSCs. However, whether ASIC1 is involved in pancreatic cancer cells-induced biological behavior re-educating of PSCs is unclear. In this study, the change of ASIC1 expression in PSCs and pancreatic cancer Panc-1 cells after indirect co-culture was detected by western blotting, and the proliferation and migration of PSCs with ASIC1 knockdown under Panc-1 cells-conditioned medium (Panc-1-CM) was assessed. The results showed that pancreatic cancer cells induced ASIC1 overexpression, and the enhanced proliferation and migration of PSCs was weakened by ASIC1 inhibition. In addition, the extracellular signal-regulated kinase (ERK) expression in PSCs remained stable, but the phosphorylated ERK (p-ERK) expression in PSCs treated with Panc-1-CM increased, which was suppressed by ASIC1 knockdown. These results indicate that ASIC1 participates in the regulation of PSCs proliferation and migration induced by cancer cells via the ERK pathway, and ASIC1 inhibition may be beneficial to pancreatic cancer treatment.

Lung cancer is among the most common cancers, and the current therapeutic strategies are still inefficient in most cases. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising biological agent for cancer treatment because of its potent pro-apoptotic effect on cancer cells. However, TRAIL also induces apoptosis in normal cells and therefore may cause toxicity to normal tissues if clinically applied. To address this issue, we inserted microRNA response elements (MREs) of miR-133a, miR-137 and miR-449a, which are all underexpressed in lung cancer cells, into an adenoviral vector to regulate TRAIL expression. This MRE-regulated vector (Ad-TRAIL-MRE) was able to express TRAIL in a lung-cancer-specific fashion. No TRAIL expression was detected in normal cells. Consistently, Ad-TRAIL-MRE exerted cytotoxicity to lung cancer cells, rather than normal cells, perhaps via inducing selective apoptosis. The selective TRAIL-mediated growth-inhibiting effect was further confirmed in a tumour xenograft model. Also, Ad-TRAIL-MRE only resulted in very low hepatotoxicity when applied. Collectively, we generated a novel TRAIL-expressing adenoviral vector that was regulated by MREs. This strategy permits TRAIL expression in a lung-cancer-specific manner and is worth further studying for clinical trials.

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