Comprehensive analysis of long noncoding RNA (lncRNA)-chromatin interactions reveals lncRNA functions dependent on binding diverse regulatory elements

Zhang, Guanxiong; Lan, Yujia; Xie, Aimin; Shi, Jian; Zhao, Hongying; Xu, Liwen; Zhu, Shiwei; Luo, Tao; Zhao, Tingting; Xiao, Yun; Li, Xia

doi:10.1074/jbc.ra119.008732

Cited by 41 publications

(22 citation statements)

References 66 publications

(64 reference statements)

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“…The function of lncRNAs is similar to that of miRNAs, which are able to regulate the expression of neighboring target genes (36,37). The present study indicated that certain lncRNAs are significantly associated with their target genes and that those lncRNAs exert their function through their predicted target genes.…”

Section: Discussionsupporting

confidence: 51%

Bioinformatics analysis of aberrantly expressed exosomal lncRNAs in oral squamous cell carcinoma (CAL‑27 vs. oral epithelial) cells

Jin

Huang

et al. 2020

Oncol Lett

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Oral squamous cell carcinoma (OSCC) is the most prevalent form of malignant tumour in the oral cavity and its early detection is critical for improving the prognosis of affected patients. The present study aimed to isolate and confirm exosomes derived from the supernatant of the OSCC cell line CAL-27 and human oral epithelial cells (HOECs), analyze long non-coding RNA (lncRNA) expression profiles and determine the diagnostic value based on bioinformatics analyses. The results indicated that the particles isolated from the supernatant of CAL-27 and HOECs were either round or oval, had a size range of 30-150 nm and were enriched with ALG-2 interacting protein X (ALIX) and tumour susceptibility 101 proteins (TSG101). These characteristics confirmed that these particles were exosomes. Three lncRNAs (NR-026892.1, NR-126435.1 and NR-036586.1) were selected as potential diagnostic biomarkers for OSCC. The expression levels of the selected lncRNAs were significantly different in CAL-27-exo vs. HOEC-exo, as well as in whole cells (CAL-27 vs. HOECs) (P<0.001). The expression levels of the three lncRNAs confirmed by quantitative PCR were consistent with the sequencing data. In conclusion, various lncRNAs were aberrantly expressed between cancerous and non-cancerous exosomes, suggesting that they may serve as biomarkers for cancer.

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Section: Discussionsupporting

confidence: 51%

Bioinformatics analysis of aberrantly expressed exosomal lncRNAs in oral squamous cell carcinoma (CAL‑27 vs. oral epithelial) cells

Jin

Huang

et al. 2020

Oncol Lett

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“…Subsequently, these miRNAs lose the ability to function as a tumor suppressor and oncogenic mRNAs are translated contributing to tumorigenesis [63]. Moreover, as several lncRNAs, which exert their functions by binding to both promoter and distal regulatory elements, NEAT1 controls 13.3% of genes in the PI3K-AKT signaling pathway by interacting with distal regulatory elements [64].…”

Section: Discussionmentioning

confidence: 99%

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

Lulli

Buccarelli

Ilari

et al. 2020

IJMS

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Glioblastoma (GBM) is the most aggressive and prevalent form of a human brain tumor in adults. Several data have demonstrated the implication of microRNAs (miRNAs) in tumorigenicity of GBM stem-like cells (GSCs). The regulatory functions of miRNAs in GSCs have emerged as potential therapeutic candidates for glioma treatment. The current study aimed at investigating the function of miR-370-3p in glioma progression, as aberrant expression of miR-370-3p, is involved in various human cancers, including glioma. Analyzing our collection of GBM samples and patient-derived GSC lines, we found the expression of miR-370-3p significantly downregulated compared to normal brain tissues and normal neural stem cells. Restoration of miR-370-3p expression in GSCs significantly decreased proliferation, migration, and clonogenic abilities of GSCs, in vitro, and tumor growth in vivo. Gene expression analysis performed on miR-370-3p transduced GSCs, identified several transcripts involved in Epithelial to Mesenchymal Transition (EMT), and Hypoxia signaling pathways. Among the genes downregulated by the restored expression of miR-370-3p, we found the EMT-inducer high-mobility group AT-hook 2 (HMGA2), the master transcriptional regulator of the adaptive response to hypoxia, Hypoxia-inducible factor (HIF)1A, and the long non-coding RNAs (lncRNAs) Nuclear Enriched Abundant Transcript (NEAT)1. NEAT1 acts as an oncogene in a series of human cancers including gliomas, where it is regulated by the Epidermal Growth Factor Receptor (EGFR) pathways, and contributes to tumor growth and invasion. Noteworthy, the expression levels of miR-370-3p and NEAT1 were inversely related in both GBM tumor specimens and GSCs, and a dual-luciferase reporter assay proved the direct binding between miR-370-3p and the lncRNAs NEAT1. Our results identify a critical role of miR-370-3p in the regulation of GBM development, indicating that miR-370-3p acts as a tumor-suppressor factor inhibiting glioma cell growth, migration and invasion by targeting the lncRNAs NEAT1, HMGA2, and HIF1A, thus, providing a potential candidate for GBM patient treatment.

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“…NEAT1 has been shown to promote tumorigenesis in several different cancers by regulating the function of several tumor suppressor miRNAs ( Prinz et al, 2019 ). NEAT1 has also been shown to regulate proliferation and fibrosis of mesangial cells, which are specialized cells in the kidney that make up mesangium of glomerulus, in diabetic nephrophathy by activating AKT/mTOR pathway ( Huang et al, 2019 ; Zhang et al, 2019 ). The physiological consequence of this regulation in cellular hypertrophy remains unclear.…”

Section: Introductionmentioning

confidence: 99%

LncRNA NEAT1 Promotes High Glucose-Induced Mesangial Cell Hypertrophy by Targeting miR-222-3p/CDKN1B Axis

Liao

Chen

Zhang

et al. 2021

Front. Mol. Biosci.

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Glomerular hypertrophy is an early morphological alteration in diabetic nephropathy. Cyclin-Dependent Kinases have been shown to be required for high glucose (HG)-induced hypertrophy; however, the upstream regulators of CDKN1B in glomerular hypertrophy remain unclear. Herein we describe a novel pathway in which Long noncoding RNA (lncRNA) NEAT1 regulates the progression of mesangial cell hypertrophy via a competing endogenous RNA (ceRNA) mechanism. Real-time PCR was performed to detect the relative NEAT1 and miR-222-3p expressions and further confirmed the relationship between NEAT1 and miR-222-3p. Cell cycle was evaluated by flow cytometry. The related mechanisms were explored by Western blot, RNA immunoprecipitation and chromatin immunoprecipitation assay. We show that NEAT1 forms double stranded RNA (dsRNA) with miR-222-3p, thus limiting miR-222-3p’s binding with CDKN1B. This release of CDKN1B mRNA leads to elevated CDKN1B protein expression, resulting in hypertrophy. In addition, we demonstrated that STAT3 which is activated by HG induces the transcription of NEAT1 by binding to its promoter. Our findings underscore an unexpected role of lncRNAs on gene regulation and introduce a new mode of proliferation regulation in mesangial cells.

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Comprehensive analysis of long noncoding RNA (lncRNA)-chromatin interactions reveals lncRNA functions dependent on binding diverse regulatory elements

Cited by 41 publications

References 66 publications

Bioinformatics analysis of aberrantly expressed exosomal lncRNAs in oral squamous cell carcinoma (CAL‑27 vs. oral epithelial) cells

Bioinformatics analysis of aberrantly expressed exosomal lncRNAs in oral squamous cell carcinoma (CAL‑27 vs. oral epithelial) cells

Mir-370-3p Impairs Glioblastoma Stem-Like Cell Malignancy Regulating a Complex Interplay between HMGA2/HIF1A and the Oncogenic Long Non-Coding RNA (lncRNA) NEAT1

LncRNA NEAT1 Promotes High Glucose-Induced Mesangial Cell Hypertrophy by Targeting miR-222-3p/CDKN1B Axis

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