LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

Sun, Tian; He, Jie; Liang, Qian; Ren, Lin; Yan, Ting; Yu, Ta Chung; Tang, Jia-Yin; Yu, Bao; Hu, Ye; Lin, Yanwei; Sun, Da; Chen, Ying Xuan; Hong, Jie; Chen, Haoyan; Zou, Weiping; Fang, Jing‐Yuan

doi:10.1158/2159-8290.cd-15-0921

Cited by 324 publications

(276 citation statements)

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“…Both KAT2A and HIST4H4 play central roles in transcriptional regulation and have been demonstrated to exert roles in gastric carcinoma [47,48]. However, their biological functions in HCC have not yet been studied.…”

Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis

Ling

Xiong

Meng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Accumulated evidence indicates that lncRNA NEAT1 has important roles in various malignant tumors. In this study, we conducted a comprehensive analysis to explore the exact role of NEAT1 in hepatocellular carcinoma (HCC). Methods: The effects of NEAT1 on cell proliferation, apoptosis, migration, and invasion were measured by in vitro experiments. The expression level and clinical value of NEAT1 in HCC was evaluated based on data from The Cancer Genome Atlas (TCGA), Oncomine, and in-house real-time quantitative (RT-qPCR). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) network analyses were conducted to investigate the potential molecular mechanisms of NEAT1. Results: NEAT1 siRNA not only inhibited proliferation, migration, and invasion of HCC cells but also induced HCC cell apoptosis. A total of four records from TCGA, Oncomine, and RT-qPCR analysis were combined to assess the expression level of NEAT1 in HCC. The pooled standard mean deviation (SMD) indicated that NEAT1 was up-regulated in HCC (SMD = 0.54; 95% CI, 0.36–0.73; P < 0.0001). The area under the curve value of the summary receiver operating characteristic curve was 0.71. NEAT1 expression was also related to race (P = 0.025) and distant metastasis (P = 0.002). Additionally, the results of GO, KEGG pathway, and PPI network analyses suggest that NEAT1 may promote the progression of HCC by interacting with several tumor-related genes (SP1, MDM4, CREBBP, TRAF5, CASP8, TRAF1, KAT2A, and HIST4H4). Conclusions: NEAT1 contributes to the deterioration of HCC and provides a potential biomarker for the diagnosis and therapy of HCC.

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Section: Discussionmentioning

confidence: 99%

LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis

Ling

Xiong

Meng

et al. 2018

Cell Physiol Biochem

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“…Metastasis-promoting capability of GClnc1 was assessed in nude mice with GES-1 and MGC 803 cells after subcutaneous implantation and injection of adenovirus expressing GClnc1 or sh GClnc1. The experiments revealed a positive impact of GClnc1 on metastasis of these cell lines to the lungs (97). MOA studies revealed that GClnc1 acts as a scaffold for WDR5 (98) and KAT2A (99).…”

Section: Metastasis-associated Lung Adenocarcinoma Transcript (Malat1mentioning

confidence: 88%

“…GClnc1 was identified by comparison of lncRNA expression profiling in gastric cancer and adjacent normal tissue and its up-regulation correlates with poor prognosis in patients with gastric cancer (97). In gastric cancer cell lines BGC 823, MKN 45 and GES-1, GClnc1 mediates proliferation and invasion as shown by a combination of ectopic expression and small interfering RNA (siRNA) experiments (97). Metastasis-promoting capability of GClnc1 was assessed in nude mice with GES-1 and MGC 803 cells after subcutaneous implantation and injection of adenovirus expressing GClnc1 or sh GClnc1.…”

Section: Metastasis-associated Lung Adenocarcinoma Transcript (Malat1mentioning

confidence: 99%

“…One of the genes affected by GClnc1 is mitochondrial superoxide dismutase (SOD2). Binding of WDR5 and KAT2A to its promoter results in its transactivation due to increased H3K4 trimethylation and H3K9 acetylation (97) (Figure 1E). SOD2 has been shown to be elevated in gastric cancer and regulation of metastasis (100,101).…”

Section: Metastasis-associated Lung Adenocarcinoma Transcript (Malat1mentioning

confidence: 99%

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Long Non-coding RNAs and their Role in Metastasis

Weidle

Birzele

Kollmorgen

et al. 2017

CGP

167

121

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Abstract.Metastasis is the major cause of death in patients with cancer. It is mediated by a multi-step process referred to as the metastatic cascade (1, 2). Initial steps include local invasion and migration, angiogenesis, epithelialmesenchymal transition (EMT) and intravasation. Tumor cells enter the circulation as single cells or circulating tumor cell clusters, are coated by platelets to escape an immune response and subsequently arrest in capillaries in distant organs as a prerequisite for extravasation. Colonization starts by homing of tumor cells in supporting niches of the organ parenchyma, followed by a latency phase which can last from several months to decades. A prerequiste for overt outgrowth of micrometastases is their adaptation to the local microenvironment and acquisition of colonisation-promoting traits (3-6). The pattern of colonized distant organs depends on the tumor type and can range from predominant spread to one organ and colonization of different types of organs sequentially or simultaneously (7). Several genes and their products have been identified to mediate crucial steps of the metastatic process such as metastasis initiation and progression, as well as organ-specific functions of metastasis (virulence) (8, 9). These gene products include proteases, chemokines, cytokines and their receptors, angiogenic factors, intracellular and transmembrane kinases, adhesion molecules, components of the extracellular matrix (ECM), GPI-linked receptors and carbohydrate metabolism-related enzymes (8, 9). More recently, an important impact of RNA-related molecules for metastasis has emerged. MicroRNAs (miRs) and other types of RNA modulate metastasis via regulatory networks (10,11). In this review we focus on the role of long non-coding RNAs (lncRNA) as promoters or inhibitors of metastasis in different tumor entities since there is an urgent need to define new targets for therapeutic intervention. With the exception of denosumab for treatment of bone metastases, all other agents evaluated in clinical studies for treatment of metastatic disease gave rise to mixed or disappointing results (6).

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“…Jingyuan Fang (Shanghai Jiao Tong University School, Shanghai, China) reported that a novel lncRNA, GClnc1, served as a scaffold of WDR5 (a key component of histone methyltransferase complex) and KAT2A histone acetyltransferase [16]. The expression of GClnc1 was associated with poor prognosis in gastric cancer.…”

Section: Noncoding Rna In Cancermentioning

confidence: 99%

Meeting Report of the Fifth International Cancer Epigenetics Conference in Beijing, China, October 2016

et al. 2017

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LncRNA GClnc1 Promotes Gastric Carcinogenesis and May Act as a Modular Scaffold of WDR5 and KAT2A Complexes to Specify the Histone Modification Pattern

Cited by 324 publications

References 50 publications

LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis

LncRNA NEAT1 Promotes Deterioration of Hepatocellular Carcinoma Based on In Vitro Experiments, Data Mining, and RT-qPCR Analysis

Long Non-coding RNAs and their Role in Metastasis

Meeting Report of the Fifth International Cancer Epigenetics Conference in Beijing, China, October 2016

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