LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers

Xin, Xiaoru; Li, Qianan; Fang, Jinyong; Zhao, Tiejun

doi:10.3389/fonc.2021.679244

Cited by 41 publications

(22 citation statements)

References 136 publications

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“…HOTAIR mediates epigenetic changes that repress genes by shuttling PRC2 and LSD1 to their targets (70). In multiple cancers HOTAIR promotes tumor growth, metastasis, migration and epithelial mesenchymal transition (70)(71)(72). HOTAIR is increased by estrogen in breast cancer cells (73), is associated with poor prognosis in endometrial cancer (74) and mediates endometrial cancer cell proliferation and invasion (75).…”

Section: Discussionmentioning

confidence: 99%

The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids

Hewitt

Wang

et al. 2022

Endocrinology

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Endometrial health is impacted by molecular processes that underlie estrogen responses. We assessed estrogen regulation of endometrial function by integrating the estrogen receptor alpha (ESR1) cistromes and transcriptomes of endometrial biopsies taken from the proliferative and mid-secretory phases of the menstrual cycle together with hormonally stimulated endometrial epithelial organoids. The cycle stage specific ESR1 binding sites were determined by ChIPseq and then integrated with changes in gene expression from RNAseq data to infer candidate ESR1 targets in normal endometrium. Genes with ESR1 binding in whole endometrium were enriched for chromatin modification and regulation of cell proliferation. The distribution of ESR1 binding sites in organoids was more distal from gene promoters when compared to primary endometrium and was more similar to the proliferative than the mid-secretory phase ESR1 cistrome. Inferred organoid estrogen/ESR1 candidate target genes impacted formation of cellular protrusions, and chromatin modification. Comparison of signaling impacted by candidate ESR1 target genes in endometrium vs. organoids reveals enrichment of both overlapping and distinct responses. Our analysis of the ESR1 cistromes and transcriptomes from endometrium and organoids provides important resources for understanding how estrogen impacts endometrial health and function.

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Section: Discussionmentioning

confidence: 99%

The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids

Hewitt

Wang

et al. 2022

Endocrinology

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“…It has also been reported that GAS5 could inhibit cell migration and invasion and promote autophagy by targeting miR-222-3p through the GAS5/PTEN-signaling pathway in colorectal cancer (53), and this targeting relationship was also predicted in the Exo-LT ceRNA network. HOTAIR is a well-known oncogenic lncRNA, and studies have determined that HOTAIR is highly up-regulated in various human cancers, such as breast cancer, lung cancer, gastric cancer, and liver cancer (54). Erdos et al found that HOTAIR binds and positively or negatively modulates the expression of genes involved in adipose tissue-speci c pathways, including adipogenesis (55).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network in exosomes from lipoma tissue reveals differential impacts on biological functions

Zhou

Wang

Shao

et al. 2022

Preprint

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Background Our previous study found that both exosomes from lipoma tissue (Exo-LT) and exosomes from adipose tissue (Exo-AT) can promote the proliferation, migration, and adipogenesis of ADSCs. There is no significant difference between Exo-LT and Exo-AT in promoting the adipogenesis of ADSCs, but Exo-LT has a stronger ability to promote the proliferation and migration of ADSCs than Exo-AT. To elucidate the reason for this difference, we envisioned to explore the gene regulation mechanism of Exo-LT's stronger pro-proliferation effect than Exo-AT by comprehensively analyzing the differential genes between Exo-LT and Exo-AT. Methods Herein, we used high-throughput sequencing technology to analyze the expression of lncRNA, miRNA, and mRNA in Exo-LT and Exo-AT and screen out significantly differentially expressed genes, and then searched mRNAs related to cell proliferation and adipogenesis in GO enrichment and KEGG pathway analysis results for subsequent targeted analysis and construction of ceRNA networks. Results A total of 10 mRNAs were screened that met both significant differential expression conditions (|logFC|>2, p < 0.05) and abundance quality control (CPM༞100), of which 6 were up-regulated in Exo-LT and 4 were down-regulated in Exo-LT. Afterwards in the ceRNA regulatory network, we noticed 5 meaningful lncRNAs that were highly correlated with cell proliferation and adipogenesis, including HOXA11-AS, GAS5, HOTAIR, MALAT1, and PVT1, among which HOXA11-AS was significantly up-regulated in Exo-LT, while GAS5, HOTAIR, MALAT1, and PVT1 were expressed at high levels in both the Exo-LT and Exo-AT group. Interestingly, our follow-up analysis found that many of the lncRNA-miRNA targeting relationships predicted by these 5 lncRNAs in the ceRNA network have been well validated in a large number of previous studies. Conclusions Our first analysis of lncRNA, miRNA, and mRNA expression profiles and ceRNA networks in Exo-LT provides a preliminary explanation for the differences between Exo-LT and Exo-AT in promoting ADSCs proliferation and adipogenesis, as well as a new theoretical basis for the formation mechanism of lipoma tissue.

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“…LncRNA HOTAIR interacts with PRC2 and induces H3K27me3-mediated repressive methylation on the promoter of tumor suppressive genes such as PTEN (phosphatase and tensin homolog) and JAM2 (junctional adhesion molecule B). It can also interact with LSD1 to induce H3K4-demethylation to activate the gene expression on the promoter of LDHA (lactate dehydrogenase A) and CCNA1 (cyclin A) genes, thereby promoting EMT and metastasis [ 133 ]. LncRNA MALAT1 sequesters miR-126-5p and enhances the expression of Slug and Twist to facilitate EMT and metastasis in colorectal cancers [ 141 ].…”

Section: Lncrnas In Human Diseasesmentioning

confidence: 99%

“…LncRNA HOTAIR recruits PRC2 to the promoter of gene encoding miR-7 to induce repressive H3K27me3 methylation. Further, the upregulation of its downstream targets such as c-Myc and Twist through miR-7/SETDB1 (SET domain bifurcated histone lysine methyl transferase 1)/STAT3 axis enhances the stemness in breast cancers [ 133 , 134 ]. The tumor suppressor lncRNA LBCS is downregulated in bladder cancers, which otherwise recruits hnRNPK and EZH2 to the promoter of SOX2 gene to induce H3K27me3 repressive tri-methylation, thus suppressing SOX2 expression [ 156 ].…”

Section: Lncrnas In Human Diseasesmentioning

confidence: 99%

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

Nadhan

Isidoro

Song

et al. 2022

Cells

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The cellular signaling network involves co-ordinated regulation of numerous signaling molecules that aid the maintenance of cellular as well as organismal homeostasis. Aberrant signaling plays a major role in the pathophysiology of many diseases. Recent studies have unraveled the superfamily of long non-coding RNAs (lncRNAs) as critical signaling nodes in diverse signaling networks. Defective signaling by lncRNAs is emerging as a causative factor underlying the pathophysiology of many diseases. LncRNAs have been shown to be involved in the multiplexed regulation of diverse pathways through both genetic and epigenetic mechanisms. They can serve as decoys, guides, scaffolds, and effector molecules to regulate cell signaling. In comparison with the other classes of RNAs, lncRNAs possess unique structural modifications that contribute to their diversity in modes of action within the nucleus and cytoplasm. In this review, we summarize the structure and function of lncRNAs as well as their vivid mechanisms of action. Further, we provide insights into the role of lncRNAs in the pathogenesis of four major disease paradigms, namely cardiovascular diseases, neurological disorders, cancers, and the metabolic disease, diabetes mellitus. This review serves as a succinct treatise that could open windows to investigate the role of lncRNAs as novel therapeutic targets.

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LncRNA HOTAIR: A Potential Prognostic Factor and Therapeutic Target in Human Cancers

Cited by 41 publications

References 136 publications

The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids

The Estrogen Receptor α Cistrome in Human Endometrium and Epithelial Organoids

Comprehensive analysis of lncRNA-miRNA-mRNA ceRNA network in exosomes from lipoma tissue reveals differential impacts on biological functions

Signaling by LncRNAs: Structure, Cellular Homeostasis, and Disease Pathology

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