Upregulation of long noncoding RNA HOTTIP promotes metastasis of esophageal squamous cell carcinoma via induction of EMT

Chen, Xuemei; Han, Hongmei; Li, Yuqi; Zhang, Qiongxia; Mo, Kailan; Chen, Size

doi:10.18632/oncotarget.12995

Cited by 60 publications

(50 citation statements)

References 13 publications

(15 reference statements)

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“…The lncRNA HOTAIR has been reported to regulate the ESCC cell cycle . Mechanistically, the lncRNA HOTTIP promotes ESCC transfer and EMT progression . LncRNA SPRY4‐IT1 promotes ESCC cell survival by activating the expression of zinc finger 703 and related proteins .…”

Section: Discussionmentioning

confidence: 99%

P53‐regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer

Yao

Zhang

et al. 2019

IUBMB Life

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The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA‐uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA‐uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK‐8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT‐PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53‐regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.

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Section: Discussionmentioning

confidence: 99%

P53‐regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer

Yao

Zhang

et al. 2019

IUBMB Life

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“…Among numerous molecules that play key roles in ESCC, lncRNAs have attracted increasing attention because their aberrant expression is associated with ESCC carcinogenesis, invasion, and metastasis . Several lncRNAs involved in ESCC have been reported, including HOTAIR, MALAT1, NMR, CASC9, PEG10, HOTTIP, SPRY4‐IT1, PCAT‐1, AK001796, and CCAT2 . HOTAIR directly downregulates the expression of WIF‐1 and activates the Wnt/β‐catenin signaling pathway to promote the migration and invasion of ESCC cells.…”

Section: Discussionmentioning

confidence: 99%

“…Dysregulation of the expression of several lncRNAs is associated with ESCC tumorigenesis, progression, and regional lymphatic metastasis . However, these lncRNAs were mostly identified in in vitro studies and lack application value in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide analysis of long non‐coding RNAs in esophageal squamous cell carcinoma reveals their potential role in invasion and metastasis

Wang

Sun

et al. 2018

Thoracic Cancer

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BackgroundA high lymphatic metastasis rate and strong local invasive ability are the key characteristics of esophageal squamous cell carcinoma (ESCC) that affect patient survival, and long non‐coding RNAs (lncRNAs) may play a crucial role. We performed genome‐wide analysis of lncRNAs to identify novel biomarkers associated with local invasion and lymphatic metastasis in ESCC.MethodsSix pairs of ESCC tumor and para‐tumor tissues were subjected to microarray analysis to identify differentially expressed lncRNAs, and 25 pairs of tissues samples were used to verify the effectiveness of screened lncRNAs using quantitative reverse transcription PCR. The correlations between verified lncRNAs and clinicopathological characteristics were analyzed to confirm specific lncRNAs associated with the local invasion and lymphatic metastasis of ESCC, and gene co‐expression analysis was used to predict potential mechanisms.ResultsMicroarray analysis identified 1850 lncRNAs with significant differential expression in ESCC. Of 22 lncRNAs selected for quantitative reverse transcription PCR verification, four were significantly upregulated and one was significantly downregulated in ESCC cancer compared to para‐cancer tissues. ENST00000508406.1 was significantly associated with T, N, and tumor node metastasis stages, and NR_037652.1 was significantly associated with N stage. Moreover, 49 lncRNA‐messenger RNA pairs were significantly associated with the two dysregulated lncRNAs and possibly involved in the regulation of local invasion and lymphatic metastasis of ESCC.ConclusionThe present genome‐wide analysis identified two novel and tumor‐specific lncRNAs for predicting ESCC local invasion and lymphatic metastasis, providing insight into the potential underlying mechanism, which warrants further investigation.

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“…Long lncRNAs are a class of ncRNAs longer than 200 nucleotides . Although the biological functions of most lncRNAs have not been characterized, there is increasing evidence that they play important roles in physiological and pathological processes, such as regulating cancer metastasis . Long ncRNAs have been reported to act as potential biomarkers that have predictive value for the survival of cancer patients.…”

Section: Introductionmentioning

confidence: 99%

A group of long noncoding RNAs identified by data mining can predict the prognosis of lung adenocarcinoma

Liao

Liu

et al. 2018

Cancer Science

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Long noncoding RNAs (lncRNA) are reported to be potential cancer biomarkers. This study aims to find new lncRNA biomarker relevant to lung adenocarcinoma. Gene expression profile and clinical data of lung adenocarcinoma and lung squamous cell carcinoma patients were downloaded from the UCSC Xena database. These data were analyzed to identify potential lncRNA prognostic biomarkers, and the candidate lncRNAs were analyzed and verified with association analysis, meta‐analysis, survival analysis, gene ontology analysis, gene set enrichment analysis, and other statistical methods. A group of 5 lncRNAs was identified from the 1965 differentially expressed (fold‐change >2) genes. Four of these 5 lncRNAs were expressed at a lower level in lung adenocarcinoma tissues and the other one at a higher level (P < .0001). A risk score model was constructed using a linear combination of the expression levels of these lncRNAs. High‐risk patients showed poorer overall survival (hazard ratio [HR] = 2.14; 95% confidence interval [CI], 1.67‐3.06, P < .0001), disease‐free survival (HR = 1.84; 95% CI, 1.26‐2.35, P = .0007), and recurrence‐free survival (HR = 1.51; 95% CI, 1.02‐2.40, P = .04). The 5‐fold cross‐validation and subsequent meta‐analysis further verified that patients in the low‐risk group had better survival (95% CI, 0.74‐1.79, Z = 4.72, P < .00001). Furthermore, both univariate and multivariate Cox regression analyses revealed that the prognostic value of these 5 lncRNAs was independent of other clinical prognostic factors. Further analysis indicated that these 5 lncRNAs might be associated with tumor metastasis. Taken together, our study suggests new prognostic lncRNA biomarkers for lung adenocarcinoma.

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Upregulation of long noncoding RNA HOTTIP promotes metastasis of esophageal squamous cell carcinoma via induction of EMT

Cited by 60 publications

References 13 publications

P53‐regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer

P53‐regulated lncRNA uc061hsf.1 inhibits cell proliferation and metastasis in human esophageal squamous cell cancer

Genome‐wide analysis of long non‐coding RNAs in esophageal squamous cell carcinoma reveals their potential role in invasion and metastasis

A group of long noncoding RNAs identified by data mining can predict the prognosis of lung adenocarcinoma

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