Probes for LONG

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.

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.

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.

Herpes simplex virus 1 (HSV-1) establishes latency in neurons and expresses long noncoding RNAs termed the latency-associated transcripts (LATs). Two previous studies using HSV-1 recombinants containing deletions in the LAT promoter revealed opposing effects of the promoter deletion regarding the heterochromatinization of latent viral genomes in mice ganglia. Confounding variables in these studies include viral strains utilized (17syn+ versus KOS), anatomical infection site (footpad versus eye) and infectious virus dose (500 versus 1 × 105 PFU), and to date the basis for the differences between the two studies remains unresolved. We recently reported that 17syn+ and KOS display distinct differences in heterochromatin levels during latency in human neurons. This raised the possibility that the discrepancy seen between the two previous studies could be explained by strain-specific differences within the LAT region. Here, we examine two recombinants containing orthologous 202 bp LAT promoter deletions, 17ΔPst and KOSΔPst, in a human neuronal model of latency and reactivation (LUHMES). We found that LUHMES neurons recapitulate previous observations in mice where deletion of the LAT promoter results in an increase in H3K27me3 deposition on the viral genome compared to the parental strain 17syn+ but a decrease compared to the parental strain KOS. We also found distinct strain-specific differences in the production of viral transcripts and proteins during latency. These results indicate that the function and/or regulation of the LATs differs between HSV-1 strains and may shed light on some discrepancies found in the literature when examining the function of the LATs. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes a lifelong infection in neuronal cells. Periodically, the virus reactivates from this latent state and causes recurrent disease. Mechanisms that control entry into and maintenance of latency are not well understood, though epigenetic posttranslational modification of histones associated with the viral genome are known to play an important role. During latency, the latency-associated transcript (LAT) is known to impact epigenetic marks, but the ultimate effect has been a point of controversy. Here, we utilize a human neuronal cell line model of HSV latency and reactivation (LUHMES) to characterize latency for two HSV-1 wild-type strains and their respective LAT promoter deletion viruses. We find that the LAT acts in a strain-specific manner to influence levels of chromatin marks, viral transcription, and viral protein production. This work highlights the need to account for strain-specific differences when characterizing the LAT's function and the dynamics of reactivation.