Probes for INS

Long non-coding RNAs (LncRNAs) are implicated in malignant progression of human cancers. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-known lncRNA, has been reported to play crucial roles in multiple malignancies including head and neck squamous cell carcinoma (HNSCC). However, the underlying mechanisms of MALAT1 in HNSCC progression remain to be further investigated. Here, we elucidated that compared with normal squamous epithelium, MALAT1 was notably upregulated in HNSCC tissues, especially in which was poorly differentiated or with lymph nodes metastasis. Moreover, elevated MALAT1 predicted unfavorable prognosis of HNSCC patients. The results of in vitro and in vivo assays showed that targeting MALAT1 could significantly weaken the capacities of proliferation and metastasis in HNSCC. Mechanistically, MALAT1 inhibited von Hippel-Lindau tumor suppressor (VHL) by activating EZH2/STAT3/Akt axis, then promoted the stabilization and activation of β-catenin and NF-κB which could play crucial roles in HNSCC growth and metastasis. In conclusion, our findings reveal a novel mechanism for malignant progression of HNSCC and suggest that MALAT1 might be a promising therapeutic target for HNSCC treatment.

Long non-coding RNAs (lncRNAs) play many important roles in gene regulation and disease pathogenesis. Here, we sought to determine that mitochondrial dynamic related lncRNA (MDRL) modulates NLRP3 inflammasome activation and apoptosis of vascular smooth muscle cells (VSMCs) and protects arteries against atherosclerosis.In vivo experiments, we applied LDLR knockout (LDLR-/-) mice fed the high-fat diet to investigate the effects of MDRL on atherosclerosis. In vitro experiments, we applied mouse aortic smooth muscle cells to determine the mechanism of MDRL in abrogating NLRP3 inflammasome and inhibiting cell apoptosis through miR-361/sequentosome 1 (SQSTM1) by TUNEL staining, quantitative RT-PCR, western blot, microribonucleoprotein immunoprecipitation, and luciferase reporter assay.Downregulated MDRL and increased NLRP3 were observed in mouse atherosclerotic plaques, accompanied with the increase of miR-361. The results showed that MDRL overexpression significantly attenuated the burden of atherosclerotic plaque and facilitated plaque stability through inhibiting NLRP3 inflammasome activation and cell apoptosis, and vice versa. Mechanically, MDRL suppressed NLRP3 inflammasome activation and VSMC apoptosis via suppressing miR-361. Furthermore, miR-361 directly bound to the 3'UTR of SQSTM1 and inhibited its translation, subsequently activating NLRP3 inflammasome. Systematic delivery of miR-361 partly counteracted the beneficial effects of MDRL overexpression on atherosclerotic development in LDLR-/- mice.In summary, MDRL alleviates NLRP3 inflammasome activation and apoptosis in VSMCs through miR-361/SQSTM1/NLRP3 pathway during atherogenesis. These data indicate that MDRL and inhibition of miR-361 represent potential therapeutic targets in atherosclerosis-related diseases.

Glioblastoma multiforme (GBM) is an aggressive, heterogeneous grade IV brain tumor. Glioblastoma stem cells (GSCs) initiate the tumor and are known culprits of therapy resistance. Mounting evidence has demonstrated a regulatory role of long non-coding RNAs (lncRNAs) in various biological processes, including pluripotency, differentiation, and tumorigenesis. A few studies have suggested that aberrant expression of lncRNAs is associated with GSCs. However, a comprehensive single-cell analysis of the GSC-associated lncRNA transcriptome has not been carried out. Here, we analyzed recently published single-cell RNA-sequencing datasets of adult human GBM tumors, GBM organoids, GSC-enriched GBM tumors, and developing human brains to identify lncRNAs highly expressed in GBM. To categorize GSC populations in the GBM tumors, we used the GSC marker genes SOX2, PROM1, FUT4, and L1CAM. We found three major GSC population clusters: radial glia, oligodendrocyte progenitor cells, and neurons. We found 10â€"100 lncRNAs significantly enriched in different GSC populations. We also validated the level of expression and localization of several GSC-enriched lncRNAs using qRT-PCR, single-molecule RNA FISH, and sub-cellular fractionation. We found that the radial glia GSC-enriched lncRNA PANTR1 is highly expressed in GSC lines and is localized to both the cytoplasmic and nuclear fractions. In contrast, the neuronal GSC-enriched lncRNAs LINC01563 and MALAT1 are highly enriched in the nuclear fraction of GSCs. Together, this study identified a panel of uncharacterized GSC-specific lncRNAs. These findings set the stage for future in-depth studies to examine their role in GBM pathology and their potential as biomarkers and/or therapeutic targets in GBM.

Understanding how long noncoding RNAs (lncRNAs) cooperate with splicing factors (SFs) in alternative splicing (AS) control is fundamental to human biology and disease. We show that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a well-documented AS-implicated lncRNA, regulates AS via two SFs, polypyrimidine tract-binding protein 1 (PTBP1) and PTB-associated SF (PSF). MALAT1 stabilizes the interaction between PTBP1 and PSF, thereby forming a functional module that affects a network of AS events. The MALAT1-stabilized PTBP1/PSF interaction occurs in multiple cellular contexts; however, the functional module, relative to MALAT1 only, has more dominant pathological significance in hepatocellular carcinoma. MALAT1 also stabilizes the PSF interaction with several heterogeneous nuclear ribonucleoparticle proteins other than PTBP1, hinting a broad role in AS control. We present a model in which MALAT1 cooperates with distinct SFs for AS regulation and pose that, relative to analyses exclusively performed for lncRNAs, a comprehensive consideration of lncRNAs and their binding partners may provide more information about their biological functions.