Long noncoding RNA LINC00673-v4 promotes aggressiveness of lung adenocarcinoma via activating WNT/β-catenin signaling

Guan, Hongyu; Zhu, Tong; Wu, Shanshan; Liu, Shihua; Liu, Bangdong; Wu, Jueheng; Cai, Junchao; Zhu, Xun; Zhang, Xin; Zeng, Mu‐Sheng; Li, Jun; Song, Erwei; Li, Mengfeng

doi:10.1073/pnas.1900997116

Cited by 78 publications

(85 citation statements)

References 49 publications

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“…LncRNAs have been shown to play important roles and to act through multiple mechanisms, including as ceRNAs, in a variety of cancers [46][47][48]. There is still some controversy regarding the role of LINC00673 in carcinogenesis, numerous studies have described LINC00673 as either a tumor suppressor or promoter [11][12][13][14][15]. Although previous studies have also identified the oncogenic role of LINC00673 was upregulation in breast cancer tissues and related with patients' prognosis [19], very little is known about the molecular mechanisms of LINC00673 in breast cancer carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have reported that LINC00673 is a potential tumor suppressor whose germline variation is associated with pancreatic cancer risk [10]. Conversely, LINC00673 was identified to play a role in tumorigenesis in a variety of malignancies [11][12][13][14][15]. A rapidly growing number of studies have suggested that cytoplasmic lncRNAs are essential mediators of intracellular signaling pathways and are involved in regulating mRNA stabilization and transport as well as microRNA sponging [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

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LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

141

103

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Background An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

Qiao

Ning

Wan

et al. 2019

J Exp Clin Cancer Res

141

103

View full text Add to dashboard Cite

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“…Due to unknown pathogenesis, the mortality of LUAD patients is still high and the treatment outcome is also unsatisfactory ( 27 ). In recent years, lncRNAs have played a more significant role in the development of tumors and the disorder of lncRNA may be considered as a crucial factor in the activities of tumors ( 28 , 29 ). We have found that lncRNA participated in 33 kinds of cancers.…”

Section: Discussionmentioning

confidence: 99%

A Seven Immune-Related lncRNAs Model to Increase the Predicted Value of Lung Adenocarcinoma

Liu

et al. 2020

Front. Oncol.

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Background Recent research has shown that immune-related lncRNA plays a crucial part in the tumor immune microenvironment. This study tried to identify immune-related lncRNAs and construct a robust prediction model to increase the predicted value of lung adenocarcinoma (LUAD). Methods RNA expression data of LUAD were download from the Cancer Genome Atlas (TCGA) database. Immune genes were acquired from the Molecular Signatures Database (MSigDB). The immune gene related lncRNAs were acquired by the “limma R” package and Cytoscape3.7.1. Cox regression analysis was applied to construct this forecast model. The prognostic model was validated by the testing cohort which was acquired by the bootstrap method. Results A total of 551 lncRNA expression profiles including 497 LUAD tissues and 54 non-LUAD tissues were obtained. A total of 331 immune genes were acquired. The result of the Cox regression analysis showed that seven lncRNAs (AC022784-1, NKILA, AC026355-1, AC068338-3, LINC01843, SYNPR-AS1, and AC123595-1) can be performed to construct the prediction model to forecast the prognosis of LUAD. Kaplan–Meier curves indicated that our prediction model can distribute LUAD patients into two different risk groups (high and low) with significant statistical significance ( P = 1.484e-07). Cox analysis and independent analysis illustrated that the seven-lncRNAs prediction model was an isolated factor by comparing it with other clinical variables. We validated the accuracy of our model in the testing dataset. Furthermore, the prognostic model also showed higher predictive efficiency than three other published prognostic models. The two different survival groups represented diverse immune features according to principal components analysis. GSEA analysis (gene set enrichment analysis) indicated that seven-lncRNAs signatures may be involved in the progression of tumorigenesis. Conclusions We have established a seven immune-related lncRNAs prediction model. This prognostic model had significant clinical significance that increased the predicted value and guided the personalized treatment for LUAD patients.

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“…Other lncRNAs that work as a suppressor include MEG3, interaction with p53 to downregulate β-catenin [260], and AK126698, negative regulation of FZD8 [221]. Alternatively, Guan and colleagues found that the overexpression of the lncRNA LINC00673-v4 was found to activate the Wnt/β-catenin pathway, noted by the enhanced interaction between DDX3 and CK1ε essentially leading to enhanced signaling of the pathway in lung adenocarcinoma cells [222]. With the overexpression of β-catenin and β-catenin transcriptional activity by SDH5 (ETC component) inhibition, cancer metabolism can be altered through the mediation of Wnt EMT and metastasis [261].…”

Section: Wnt/β-cateninmentioning

confidence: 99%

Non-Coding RNAs in Lung Tumor Initiation and Progression

Santos

Moreno

Zhang

2020

IJMS

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Lung cancer is one of the deadliest forms of cancer affecting society today. Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), through the transcriptional, post-transcriptional, and epigenetic changes they impose, have been found to be dysregulated to affect lung cancer tumorigenesis and metastasis. This review will briefly summarize hallmarks involved in lung cancer initiation and progression. For initiation, these hallmarks include tumor initiating cells, immortalization, activation of oncogenes and inactivation of tumor suppressors. Hallmarks involved in lung cancer progression include metastasis and drug tolerance and resistance. The targeting of these hallmarks with non-coding RNAs can affect vital metabolic and cell signaling pathways, which as a result can potentially have a role in cancerous and pathological processes. By further understanding non-coding RNAs, researchers can work towards diagnoses and treatments to improve early detection and clinical response.

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Long noncoding RNA LINC00673-v4 promotes aggressiveness of lung adenocarcinoma via activating WNT/β-catenin signaling

Cited by 78 publications

References 49 publications

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

A Seven Immune-Related lncRNAs Model to Increase the Predicted Value of Lung Adenocarcinoma

Non-Coding RNAs in Lung Tumor Initiation and Progression

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