Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

Gu, Jingtao; Zhang, Bo; An, Rui; Qian, Weikun; Liu, Han; Duan, Wanxing; Wang, Zheng; Ma, Qingyong

doi:10.3390/cancers14164009

Cited by 23 publications

(13 citation statements)

References 167 publications

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“…According to the literatures high expression of NEAT1 promotes cell proliferation, migration, invasion and inhibition of apoptosis in various cancers, including OS. [61][62][63] Our results stated the other way around which is NEAT1 poorly expressed in the osteoblastic OS cells of the OS patients and osteosarcoma cell lines compared to osteoblasts.…”

Section: Discussionsupporting

confidence: 51%

Single-Cell Transcriptome Analysis Reveals Paraspeckles Expression in Osteosarcoma Tissues

et al. 2022

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Nuclear paraspeckles are subnuclear bodies contracted by nuclear-enriched abundant transcript 1 (NEAT1) long non-coding RNA, localised in the interchromatin space of mammalian cell nuclei. Paraspeckles have been critically involved in tumour progression, metastasis and chemoresistance. To this date, there are limited findings to suggest that paraspeckles, NEAT1 and heterogeneous nuclear ribonucleoproteins (hnRNPs) directly or indirectly play roles in osteosarcoma progression. Herein, we analysed NEAT1, paraspeckle proteins (SFPQ, PSPC1 and NONO) and hnRNP members (HNRNPK, HNRNPM, HNRNPR and HNRNPD) gene expression in 6 osteosarcoma tumour tissues using the single-cell RNA-sequencing method. The normalised data highlighted that the paraspeckles transcripts were highly abundant in osteoblastic OS cells, except NEAT1, which was highly expressed in myeloid cell 1 and 2 subpopulations.

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Section: Discussionsupporting

confidence: 51%

Single-Cell Transcriptome Analysis Reveals Paraspeckles Expression in Osteosarcoma Tissues

et al. 2022

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“…The function of one nuclear lncRNA is believed to be achieved through transcriptional regulation via indirect or direct binding to transcriptional factors or to a genomic DNA sequence [31]. For example, during the last few years, a nuclear lncRNA called NEAT1 (Nuclear-Enriched Abundant Transcript 1) has recently gained considerable attention due to its important contributions to gene regulation through NEAT1-binding proteins, such as enzymes, transcription factors, and receptors [32,33]. RegRNA 2.0 [34] is an integrated web server for identifying functional RNA motifs in an input sequence, which is often used for predicting the potential binding of lncRNAs to transcriptional factors or microRNAs [35].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA LOC339059 Attenuates IL-6/STAT3-Signaling-Mediated PDL1 Expression and Macrophage M2 Polarization by Interacting with c-Myc in Gastric Cancer

Han,

Ding,

Wang

et al. 2023

Cancers

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Background: Long non-coding RNA (lncRNA) was identified as a novel diagnostic biomarker in gastric cancer (GC). However, the functions of lncRNAs in immuno-microenvironments have not been comprehensively explored. In this study, we explored a critical lncRNA, LOC339059, that can predict the clinical prognosis in GC related to the modulation of PD-L1 and determined its influence upon macrophage polarization via the IL-6/STAT3 pathway. Methods: To date, accumulating evidence has demonstrated that the dysregulation of LOC339059 plays an important role in the pathological processes of GC. It acts as a tumor suppressor, regulating GC cell proliferation, migration, invasion, tumorigenesis, and metastasis. A flow cytometry assay showed that the loss of LOC339059 enhanced PDL1 expression and M2 macrophage polarization. RNA sequencing, RNA pull-down, RNA immunoprecipitation, Chip-PCR, and a luciferase reporter assay revealed the pivotal role of signaling alternation between LOC339059 and c-Myc. Results: A lower level of LOC339059 RNA was found in primary GC tissues compared to adjacent tissues, and such a lower level is associated with a poorer survival period (2.5 years) after surgery in patient cohorts. Moreover, we determined important immunological molecular biomarkers. We found that LOC339059 expression was correlated with PD-L1, CTLA4, CD206, and CD204, but not with TIM3, FOXP3, CD3, C33, CD64, or CD80, in a total of 146 GC RNA samples. The gain of LOC339059 in SGC7901 and AGS inhibited biological characteristics of malignancy, such as proliferation, migration, invasion, tumorigenesis, and metastasis. Furthermore, our data gathered following the co-culture of THP-1 and U937 with genomic GC cells indicate that LOC339059 led to a reduction in the macrophage cell ratio, in terms of CD68+/CD206+, to 1/6, whereas the selective knockdown of LOC339059 promoted the abovementioned malignant cell phenotypes, suggesting that it has a tumor-suppressing role in GC. RNA-Seq analyses showed that the gain of LOC339059 repressed the expression of the interleukin family, especially IL-6/STAT3 signaling. The rescue of IL-6 in LOC339059-overexpressing cells reverted the inhibitory effects of the gain of LOC339059 on malignant cell phenotypes. Our experiments verified that the interaction between LOC339059 and c-Myc resulted in less c-Myc binding to the IL-6 promoter, leading to the inactivation of IL-6 transcription. Conclusions: Our results establish that LOC339059 acts as a tumor suppressor in GC by competitively inhibiting c-Myc, resulting in diminished IL-6/STAT3-signaling-mediated PDL1 expression and macrophage M2 polarization.

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“…Different reports suggest that NEAT1_V1 translocates into the cytoplasm and is not an essential component of paraspeckles, whereas NEAT1_V2 resides in the nucleus and is mainly involved in the paraspeckle formation [26]. It is possible that following translocation, the NEAT1_V1 level increases in the cytoplasm and gets released from the cells through different mechanisms (possibly through exosomes) in HCV-induced disease progression [51]. Hence, the increase in the total NEAT1 levels in serum samples could be solely due to NEAT1_V1.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis

Tripathi

Pal

Ghosh

et al. 2022

Journal of General Virology

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Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9–5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9–5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9–5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.

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Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer

Cited by 23 publications

References 167 publications

Single-Cell Transcriptome Analysis Reveals Paraspeckles Expression in Osteosarcoma Tissues

Single-Cell Transcriptome Analysis Reveals Paraspeckles Expression in Osteosarcoma Tissues

Long Non-Coding RNA LOC339059 Attenuates IL-6/STAT3-Signaling-Mediated PDL1 Expression and Macrophage M2 Polarization by Interacting with c-Myc in Gastric Cancer

LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis

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