LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1

Zhang, Xiaona; Zhou, Yanchun; Chen, Shaoying; Li, Wei; Chen, Weibing; Gu, Wei

doi:10.1038/s41389-019-0182-7

Cited by 56 publications

(44 citation statements)

References 33 publications

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“…Therefore, there is a demand for sensitive and robust molecular markers to assess M1 and M2 macrophages that will advance our understanding of unique lncRNAs with M1/M2 specific expression. LncRNAs exhibit cell-specific expression (11,12,18) and regulate epigenetic (histone modification and DNA methylation), post-transcription (RNA processing and mRNA stability) and translation pathways to govern multiple aspects of cellular functions (33)(34)(35)(36)(37)(38). Therefore, in this study, we have profiled lncRNAs (using lncRNA PCR array) in sorted CD14 + monocytes and in vitro differentiated M2j (via M-CSF treatment) in the absence of any pro-and anti-inflammatory cytokine.…”

Section: Discussionmentioning

confidence: 99%

Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

et al. 2020

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Macrophages (Mφ) are immune cells that exhibit remarkable functional plasticity. Identification of novel endogenous factors that can regulate plasticity and innate immune functions of Mφ will unravel new strategies to curb immune-related diseases. Long non-coding RNAs (lncRNAs) are a class of endogenous, non-protein coding, regulatory RNAs that are increasingly being associated with various cellular functions and diseases. Despite their ubiquity and abundance, lncRNA-mediated epigenetic regulation of Mφ polarization and innate immune functions is poorly studied. This study elucidates the regulatory role of lncRNAs in monocyte to Mφ differentiation, M1/M2 dichotomy and innate immune responses. Expression profiling of eighty-eight lncRNAs in monocytes and in vitro differentiated M2 Mφ identified seventeen differentially expressed lncRNAs. Based on fold-change and significance, we selected four differentially expressed lncRNAs viz., RN7SK, GAS5, IPW, and ZFAS1 to evaluate their functional impact. LncRNA knockdown was performed on day 3 M2 Mφ and the impact on polarization was assessed on day 7 by surface marker analysis. Knockdown of RN7SK and GAS5 showed downregulation of M2 surface markers (CD163, CD206, or Dectin) and concomitant increase in M1 markers (MHC II or CD23). RN7SK or GAS5 knockdown showed no significant impact on CD163, CD206, or CD23 transcripts. M1/M2 markers were not impacted by IPW or ZFAS1 knockdown. Functional regulation of antigen uptake/processing and phagocytosis, two central innate immune pathways, by candidate lncRNA was assessed in M1/M2 Mφ. Compared to scramble, enhanced antigen uptake and processing were observed in both M1/M2 Mφ transfected with siRNA targeting GAS5 and RN7SK but not IPW and ZFAS1. In addition, knockdown of RN7SK significantly augmented uptake of labelled E. coli in vitro by M1/M2 Mφ, while no significant difference was in GAS5 silencing cells. Together, our results highlight the instrumental role of lncRNA (RN7SK and GAS5)-mediated epigenetic regulation of macrophage differentiation, polarization, and innate immune functions.

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Section: Discussionmentioning

confidence: 99%

Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

et al. 2020

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“…Another lncRNA acting as a ceRNA that affects mRNA stability is MACC1 Antisense RNA 1 ( MACC1-AS1 ), an intronic antisense lncRNA located between the fourth and fifth exon of MACC1 , a transcriptional regulator of epithelial-mesenchymal transition (EMT) [ 55 ] that enhances gastric tumor progression [ 56 ]. It shares binding sites for miR-384 and miR-145-3p within PTN and c-Myc transcripts respectively, which are two well-known oncogenic genes [ 57 ].…”

Section: Lncrnas Affecting Mrna Stability Via Mirna Blockagementioning

confidence: 99%

The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

Sebastian-delaCruz

González-Moro

Olazagoitia-Garmendia

et al. 2021

ncRNA

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mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

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“…MIR2052HG binds to EGR1 and promotes its recruitment to the promoter region of LMTK3 in ERα-positive BC 7 . MACC1-AS1 competitively interacted with PTBP1 protein to regulate cell growth 8 . LINC01355 interacted with FOXO3 protein to repress transcription of CCND1 and to block BC growth and progression 9 .…”

Section: Introductionmentioning

confidence: 99%

M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2

et al. 2020

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As a common female malignancy, triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancers (BC). This study further studied the role of long noncoding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) in TNBC. Functional assays, including EdU, wound healing, transwell, and immunofluorescence staining, revealed the effect of PCAT6 on cell proliferation, migration, and EMT process. The tube-formation assay disclosed the function of PCAT6 on angiogenesis. In vivo assays were also established to explore the impact of PCAT6 on tumor growth and microangiogenesis. The results revealed that PCAT6 boosted TNBC cell proliferation, migration, and angiogenesis both in vitro and in vivo. Then, this study unveiled that M2 macrophage secreted VEGF to stimulate the upregulation of PCAT6, thus promoting angiogenesis in TNBC. Next, through bioinformatics analysis and mechanism assays, we identified that PCAT6 positively regulated VEGFR2 expression via ceRNA pattern and then participated in VEGFR/AKT/mTOR signaling pathway to accelerate angiogenesis. Moreover, PCAT6 bound USP14, a deubiquitinase, to induce the deubiquitination of VEGFR2. On the whole, M2 macrophage-induced upregulation of PCAT6 facilitates TNBC tumorigenesis through modulation of VEGFR2 expression via ceRNA and deubiquitination patterns.

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LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1

Cited by 56 publications

References 33 publications

Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

M2 macrophage-induced lncRNA PCAT6 facilitates tumorigenesis and angiogenesis of triple-negative breast cancer through modulation of VEGFR2

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