Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma

Wang, Wenjian; He, Xiaotian; Zheng, Zhiyuan; Ma, Xiaofan; Wu, Duoguang; Wang, Minghui

doi:10.1186/s12943-017-0643-6

Cited by 105 publications

(74 citation statements)

References 29 publications

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“…LncRNAs, especially circulating ones, are stable and accessible and are considered potential diagnostic or prognostic markers in some types of cancer [24-26]. Clinically, overexpression of LncDQ has been observed in active CD and correlates with disease severity [15].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Zeng

Lin

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long noncoding RNAs (lncRNAs) are key regulators of cancer initiation and progression. In this study, we investigated the clinical value and functional role of LncRNA DQ786243 (LncDQ) in the pathogenesis of hepatocellular carcinoma (HCC). Methods: To investigate the expression level of LncDQ in HCC, we performed quantitative real-time PCR using total RNA extracted from HCC tumor tissues and their matched non-neoplastic counterparts, as well as from the serum of HCC patients and healthy volunteers. The correlation of LncDQ expression with clinicopathologic features and prognosis was analyzed. The functional role of LncDQ in cell proliferation, migration, and invasion were evaluated by MTT cell viability, wound healing, and transwell assays in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays were performed to analyze the potential mechanism of LncDQ in HCC cells. Results: LncDQ was upregulated in both HCC tissue samples and serum and was correlated with low survival rate and adverse clinical pathological characteristics. Multivariate analysis demonstrated that LncDQ expression was an independent prognostic factor for HCC. The area under the receiver operating characteristic curve was 0.804 with a sensitivity of 0.72 and a specificity of 0.8. Knockdown of LncDQ induced inhibition of cell proliferation, migration, and invasion in vitro and in vivo. Mechanistically, LncDQ regulated the epithelial–mesenchymal transition pathway by interacting with EZH2, to epigenetically repress the expression of E-cadherin in HCC cells. Conclusions: Taken together, the results of our study indicate that LncDQ plays a critical role in HCC progression, and may serve as a potential diagnostic and prognostic biomarker for HCC.

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Section: Discussionmentioning

confidence: 99%

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Zeng

Lin

et al. 2018

Cell Physiol Biochem

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“…Long non‐coding RNAs are a family of RNAs that have no coding capacity however still exhibit the ability to play a crucial role in various biological regulatory processes such as a performance as a competing endogenous RNA (ceRNA) influencing post‐transcriptional regulation by interfering the pathways of microRNA (miRNA or miR) . A previous study revealed the diagnostic potential of serum lncRNA HOX transcript antisense RNA (HOTAIR) as a promising biomarker for oesophageal squamous cell carcinoma . HOTAIR is a 2148‐nucleotide‐long lncRNA that has been shown to participate in the development of the physiological epidermis as well as the progression of cancer, and potentially as a regulator of tumour suppressor genes .…”

Section: Introductionmentioning

confidence: 99%

“…10 A previous study revealed the diagnostic potential of serum lncRNA HOX transcript antisense RNA (HOTAIR) as a promising biomarker for oesophageal squamous cell carcinoma. 11 HOTAIR is a 2148-nucleotide-long lncRNA that has been shown to participate in the development of the physiological epidermis as well as the progression of cancer, and potentially as a regulator of tumour suppressor genes. 12 Apart from lncRNA, accumulating evidence has highlighted the crucial inhibitory role of miRs in blocking the development of oesophageal cancer, such as microRNA-204 (miR-204), which performs as a tumour suppressor.…”

Section: Introductionmentioning

confidence: 99%

Down‐regulation of long non‐coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up‐regulation of microRNA‐204

Wang

Tan²,

Zhuang³

et al. 2019

J Cellular Molecular Medi

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Oesophageal cancer is a progressive tumour with high mortality. However, therapies aimed at treating oesophageal cancer remain relatively limited. Accumulating studies have highlighted long non‐coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR), microRNA‐204 (miR‐204) and homeobox C8 (HOXC8) in the progression of oesophageal cancer. Herein, we tried to demonstrate the function of HOTAIR, miR‐204 and HOXC8 in oesophageal cancer and their relationship. Differentially expressed genes involved in oesophageal cancer were identified. The endogenous expression of HOTAIR and miR‐204 in oesophageal cancer cell lines was altered to elucidate their effects and to identify the interaction among HOTAIR, miR‐204 and HOXC8. We also explored the underlying regulatory mechanisms of HOTAIR and miR‐204 with siRNA against HOTAIR, miR‐204 mimic or miR‐204 inhibitor. Cell proliferation, migration, invasion and apoptosis were subsequently detected. Xenograft in nude mice was induced to evaluate tumourigenicity. miR‐204 was down‐regulated, while HOTAIR and HOXC8 were up‐regulated in the oesophageal cancer tissues. HOTAIR could competitively bind to miR‐204 and miR‐204 could further target HOXC8. The oesophageal cancer cells treated with si‐HOTAIR or miR‐204 mimic exhibited decreased expression levels of HOXC8, Vimentin and MMP‐9, but increased E‐cadherin level. Silenced HOTAIR or elevated miR‐204 inhibited proliferation, migration and invasion, along with stimulated apoptosis of oesophageal cancer cells. In summary, our results show that lncRNA HOTAIR could specifically bind to miR‐204 as a competing endogenous RNA and regulate miR‐204 and HOXC8. Hence, down‐regulation of HOTAIR could inhibit progression of oesophageal cancer, indicating a novel target for oesophageal cancer treatment.

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“…LncRNA is a class of transcript with more than 200 nucleotides in length, but do not encode proteins . Aberrant expressions of lncRNAs have been revealed in various pathological status, particular in cancers . Furthermore, lncRNAs also play important roles in various pathophysiological processes, including cancers .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] Aberrant expressions of lncRNAs have been revealed in various pathological status, particular in cancers. [10][11][12][13] Furthermore, lncRNAs also play important roles in various pathophysiological processes, including cancers. [14][15][16][17][18] In NSCLC, several lncRNAs are reported to participate in tumourigenesis and/or development of NSCLC.…”

mentioning

confidence: 99%

A positive feedback loop between ZNF205‐AS1 and EGR4 promotes non‐small cell lung cancer growth

Lin

Yang

et al. 2018

J Cellular Molecular Medi

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Accumulating evidences revealed that long noncoding RNAs (lncRNAs) are frequently implicated in non‐small cell lung cancer (NSCLC). Herein, we reported the identification of a novel NSCLC‐associated functional lncRNA ZNF205 antisense RNA 1 (ZNF205‐AS1). ZNF205‐AS1 was increased in NSCLC tissues and cell lines, and associated with poor prognosis of NSCLC patients. Bioinformatics prediction, combined with experimental verification revealed that early growth response 4 (EGR4) directly bound to ZNF205‐AS1 promoter, increased the promoter activity of ZNF205‐AS1, and activated ZNF205‐AS1 transcription. Intriguingly, ZNF205‐AS1 transcript directly interacted with EGR4 mRNA, increased EGR4 mRNA stability, and up‐regulated EGR4 expression via RNA‐RNA interaction. Thus, ZNF205‐AS1 and EGR4 formed a positive feedback loop. Through regulating EGR4, ZNF205‐AS1 activated its own promoter activity. EGR4 was also increased in NSCLC and the expression of ZNF205‐AS1 was significantly positively correlated with EGR4 in NSCLC tissues. Gain‐of‐function and loss‐of‐function assays demonstrated that both ZNF205‐AS1 and EGR4 promoted NSCLC cell growth in vitro and NSCLC tumour growth in vivo. Concurrently depleting ZNF205‐AS1 and EGR4 more significantly repressed NSCLC tumour growth in vivo. Collectively, our study demonstrated that the positive feedback loop between ZNF205‐AS1 and EGR4 promotes NSCLC growth, and implied that targeting this feedback loop may be promising therapeutic strategy for NSCLC.

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Serum HOTAIR as a novel diagnostic biomarker for esophageal squamous cell carcinoma

Cited by 105 publications

References 29 publications

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Upregulation of LncDQ is Associated with Poor Prognosis and Promotes Tumor Progression via Epigenetic Regulation of the EMT Pathway in HCC

Down‐regulation of long non‐coding RNA HOTAIR inhibits invasion and migration of oesophageal cancer cells via up‐regulation of microRNA‐204

A positive feedback loop between ZNF205‐AS1 and EGR4 promotes non‐small cell lung cancer growth

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