Targeting LINC070974 inhibits lung adenocarcinoma cell proliferation and progression by interacting with Y-box binding protein 1.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. Increasing evidence suggests that long noncoding RNAs play crucial roles in lung cancer pathogenesis. We previously identified a novel lncRNA, LINC070974, which is associated with tumor cell proliferation. In the present study, we find that knockdown of LINC070974 inhibits cell proliferation, migration and invasion as well as tumor formation both in vitro and in nude mice. LINC070974 silencing also improves cisplatin efficacy in A549/DDP cells. The function of LINC070974 may depend on its interaction with YBX1. Knockdown of LINC070974 reduces the recruitment of YBX1 to the CCND1 promoter and delays tumor progression through its coregulatory genes, which are mainly involved in the p53 signaling pathway. We utilize nebulized inhalation to deliver siRNAs targeting LINC070974 and find that LINC070974 significantly prevents tumor metastasis and growth in lung tissues. These findings reveal the role of LINC070974 in lung cancer and suggest a promising therapeutic approach involving siRNA inhalation.

Hepatic transcriptome analysis from HFD-fed mice defines a long noncoding RNA regulating cellular cholesterol levels.

To elucidate the transcriptomic changes of long noncoding RNAs (lncRNAs) in high-fat diet (HFD)-fed mice, we defined their hepatic transcriptome by RNA sequencing. Aberrant expression of 37 representative lncRNAs and 254 protein-coding RNAs was observed in the livers of HFD-fed mice with insulin resistance compared with the livers from control mice. Of these, 24 lncRNAs and 179 protein-coding RNAs were upregulated, whereas 13 lncRNAs and 75 protein-coding RNAs were downregulated. Functional analyses showed that the aberrantly expressed protein-coding RNAs were enriched in various lipid metabolic processes and in the insulin signaling pathway. Genomic juxtaposition and coexpression patterns identified six pairs of aberrantly expressed lncRNAs and protein-coding genes, consisting of five lncRNAs and five protein-coding genes. Four of these protein-coding genes are targeted genes upregulated by PPARα. As expected, the corresponding lncRNAs were significantly elevated in AML12 cells treated with palmitic acid or the PPARα agonist, WY14643. In Hepa1-6 cells, knockdown of NONMMUG027912 increased the cellular cholesterol level, the expression of cholesterol biosynthesis genes and proteins, and the HMG-CoA reductase activity. This genome-wide profiling of lncRNAs in HFD-fed mice reveals one lncRNA, NONMMUG027912, which is potentially regulated by PPARα and is implicated in the process of cholesterol biosynthesis.