Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer

Zhao, Rui; Zhang, Yanli; Zhang, Xin; Yang, Yongmei; Zheng, Xin; Li, Xiaohui; Liu, Yingjie; Zhang, Yi

doi:10.1186/s12943-018-0817-x

Cited by 229 publications

(164 citation statements)

References 20 publications

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“…35 In the last decade, the role of exosomes in stroke has been attracted much attention. 37 However, at present, the role of exosomal HOTTIP in ischemic stroke has not been found. 37 However, at present, the role of exosomal HOTTIP in ischemic stroke has not been found.…”

Section: Discussionmentioning

confidence: 91%

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Wang

Zhao

et al. 2018

J of Cellular Biochemistry

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HOXA transcript at the distal tip (HOTTIP), which is a long noncoding RNA, plays an important role in multiple cancers and in coronary artery disease. Elevated microRNA-143 (miR-143) expression causes impaired glucose uptake that is responsible for the ischemic cerebral injury. However, the role and mechanism of HOTTIP in ischemic stroke are still unknown. The expression of HOTTIP and miR-143 was first detected in mouse models of transient middle cerebral artery occlusion and in primary neurons exposed to oxygen-glucose deprivation (OGD). We used gain-of function and loss-of function approaches in vitro to investigate the effect and mechanism of HOTTIP on ischemic stroke by evaluating cell viability, apoptosis, and glycolytic metabolism of neurons exposed to OGD. The HOTTIP expression was decreased, whereas miR-143 increased in experimental ischemic stroke models. Overexpression of HOTTIP by the pcDNA3.1-HOTTIP plasmid significantly increased cell viability, glucose uptake, and the expression of hexokinase 2 (HK-2) and pyruvate kinase M2 that were reduced by OGD insult. The HOTTIP overexpression also diminished OGD induced the apoptosis and the caspase-3 activity of neurons. The miR-143 mimic reversed these effects, and anti-miR-143 enhanced them. In addition, we found that HOTTIP could function as a competing endogenous RNA for miR-143 to modulate HK-2 expression. In conclusion, the HOTTIP expression was reduced in ischemic stroke. The HOTTIP overexpression attenuated OGD-induced neuronal injury and imbalanced glycolytic metabolism by sponging miR-143, resulting in the de-repression of its endogenous target HK-2. Taken together, these findings improve understanding of the pathogenesis of ischemic stroke.

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Section: Discussionmentioning

confidence: 91%

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Wang

Zhao

et al. 2018

J of Cellular Biochemistry

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“…Kong et al demonstrated that LINC00460 contributes to the progression of nasopharyngeal carcinoma by regulating the miR‐145‐5p/IL6 signal pathway. HOTTIP is considered an oncogene and a potential target in multiple cancers, including colorectal cancer, breast carcinoma, and gastric cancer . To the best of our knowledge, few studies have assessed LINC00443, LINC00472, WT1‐AS, AC016773.1, TRIM36‐IT1, and NALCN‐AS1 in cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction and comprehensive analysis of dysregulated long non‐coding RNA‐associated competing endogenous RNA network in clear cell renal cell carcinoma

Wang

Zhang

et al. 2018

J of Cellular Biochemistry

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Objective This study aimed to assess the long noncoding RNA (lncRNA)‐microRNA (miRNA)‐messenger RNA (mRNA) regulatory network in clear cell renal cell carcinoma (ccRCC) by gene expression analyses. Materials and Methods LncRNA, miRNA, and mRNA expression profiles in ccRCC were obtained from The Cancer Genome Atlas. Differentially expressed lncRNAs, mRNAs (cut‐off: |log 2 [fold change, FC])| > 2.0 and adjusted P < 0.01) and miRNAs (|log 2FC| > 1.5 and adjusted P < 0.01) were unveiled using R. Cox regression analysis was performed to identify prognostic factors of ccRCC related to overall survival (OS). A protein‐protein interaction (PPI) network was constructed for differentially expressed mRNAs (DEmRNAs) by Search Tool for the Retrieval of Interacting Genes (STRING). Key hub genes were screened from top 300 DEmRNAs. LncRNA‐miRNA and miRNA‐mRNA regulatory network were constructed and combined into the competing endogenous RNA regulatory network. Gene ontology biological terms were screened by STRING; Kyoto Encyclopedia of Genes and Genomes pathways were identified using the “clusterProfiler” package in R. Results A total of 2331, 1517, and 83 DEmRNAs, lncRNAs, and miRNAs were identified, respectively. Eleven lncRNAs (AC016773.1, HOTTIP, LINC00460, NALCN‐AS1, PVT1, TRIM36‐IT1, WT1‐AS, COL18A1‐AS1, LINC00443, LINC00472, and TCL6), three miRNAs (hsa‐mir‐21, hsa‐mir‐144, and hsa‐mir‐155), and three mRNAs (COL4A4, NOD2, and GOLGA8B) were associated with OS. Specifically, four lncRNAs (PVT1, LINC00472, TCL6, and WT1‐AS1) and one mRNA (Collagen Type IV Alpha 4 Chain) were verified as independent prognostic factors by Gene Expression Profiling Interactive Analysis. Eleven key hub genes were obtained by PPI analysis. “Cell adhesion molecules (CAMs),” “chemical carcinogenesis,” and “cytokine‐cytokine receptor interaction” were significantly enriched in the network. Conclusion The findings clarify the pathogenesis of ccRCC and might provide potential therapeutic targets.

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“…HOTTIP knockdown impedes cell viability, proliferation, invasion, and angiogenesis in human cancer cells, therefore it is been identified as an oncogenic long noncoding RNA (lncRNA). In addition, HOTTIP overexpression is in association with poor prognosis in cancers . HOTTIP expression is regulated by miR‐125, miR‐192, and miR‐204 .…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

Zheng

Mao

Dong

et al. 2018

J Cellular Molecular Medi

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HOXA transcript at the distal tip (HOTTIP) has been shown to be up‐regulated in a variety of cancers and is identified as an oncogenic long noncoding RNA. However, the biological role of HOTTIP in liver fibrosis is unclear. Here, we reported that HOTTIP was specifically overexpressed in activated hepatic stellate cells (HSCs). HOTTIP knockdown suppressed the activation and proliferation of HSCs. Luciferase reporter assay showed that HOTTIP and serum response factor (SRF) were targets of miR‐150. RNA binding protein immunoprecipitation assay indicated the interaction between miR‐150 and HOTTIP. Further study revealed that HOTTIP increased SRF expression as a competing endogenous RNA for miR‐150, thus prompting HSC activation. Taken together, we provide a novel HOTTIP‐miR‐150‐SRF signalling cascade in liver fibrosis.

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Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer

Cited by 229 publications

References 20 publications

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Long noncoding RNA HOTTIP alleviates oxygen‐glucose deprivation‐induced neuronal injury via modulating miR‐143/hexokinase 2 pathway

Construction and comprehensive analysis of dysregulated long non‐coding RNA‐associated competing endogenous RNA network in clear cell renal cell carcinoma

Long noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells

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