Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

Zhang, Hua; Zhao, Lei; Wang, Yingxue; Xi, Mian; Liu, Shiliang; Luo, Lingaï

doi:10.1007/s13277-015-3645-2

Cited by 87 publications

(100 citation statements)

References 27 publications

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“…A flow diagram of the identification and selection of studies is shown in Figure 1. After evaluation, five studies including 460 patients were finally enrolled for further analysis [11, 14–16, 21]. The sample size ranged from 52 to 156 patients.…”

Section: Resultsmentioning

confidence: 99%

“…The HOXA transcript at the distal tip (HOTTIP) lncRNA, located at the 5′end of the HOXA cluster, was recently functionally characterized [10]. Increased HOTTIP expression has been reported in tongue squamous cell carcinoma [11], lung cancer [12], pancreatic cancer [13], hepatocellular carcinoma [14], osteosarcoma [15], gastric cancer [16], glioma [17] and prostate cancer [18]. In these tumors, HOTTIP may serve as a potential oncogene and be an adverse prognostic factor in patients.…”

Section: Introductionmentioning

confidence: 99%

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The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

et al. 2016

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Although a few studies have assessed the prognostic value of long noncoding RNA HOTTIP in patients with malignant tumors, the relationship between HOTTIP and clinical outcome of breast cancer remains elusive. The aim of this study is to explore the prognostic significance of HOTTIP in breast cancer patients. A meta-analysis was performed to involve the eligible studies to investigate the association of HOTTIP expression level with outcome in cancer patients. Pooled hazard ratios (HRs) and 95% confidence interval (CI) of HOTTIP for cancer survival were calculated. Five relevant articles involving 460 patients with various solid carcinomas were included in this meta-analysis. For overall survival, high HOTTIP expression could significantly predict worse outcome with the pooled HR of 2.29 (95 % CI 1.72–3.03, P < 0.00001). Furthermore, Gene Expression Omnibus was performed to evaluate the association of HOTTIP expression with the prognosis in breast cancer patients. It was also found an indication that high HOTTIP expression was associated with worse survival in breast cancer patients by microarray analysis (GSE20711, GSE16446 and GSE9195). Finally, association between HOTTIP levels and clinicopathological factors and prognosis was also analyzed in an independent validation cohort including 100 breast cancer cases. HOTTIP expression was correlated with tumor size (P=0.025), lymph node status (P=0.009) and TNM stage (P=0.0001) in the breast cancer validation cohort. The Kaplan-Meier survival curves indicated that breast cancer patients with high HOTTIP expression had worse overall survival (P=0.0139) and disease-free survival (P=0.0003). Multivariate survival analysis based on the Cox proportional hazards model showed that HOTTP is considered as an independent prognostic factor in breast cancer patients. Together, our combined results suggest that high HOTTIP expression may be serving as an unfavorable prognosis predictor for breast cancer patients.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

et al. 2016

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“…The interaction between HOTTIP and the WDR5–mixed lineage leukemia (MLL) complex increases histone H3 lysine 4 trimethylation and activates the expression of multiple 5′-HoxA genes [19]. Recent reports have shown that HOTTIP is associated with cancer metastasis and is a negative prognostic factor in patients with liver and tongue cancer [20, 21]. In addition, HOTTIP expression promotes cancer progression and drug resistance by regulating HoxA13 in pancreatic cancer [22].…”

Section: Introductionmentioning

confidence: 99%

Oncogenic function of the homeobox A13-long noncoding RNA HOTTIP-insulin growth factor-binding protein 3 axis in human gastric cancer

et al. 2016

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To study the mechanisms of gastric tumorigenesis, we have established CSN cell line from human normal gastric mucosa, and CS12, a tumorigenic and invasive gastric cancer cell line from CSN passages. Many stem cell markers were expressed in both CSN and CS12 cells, but LGR5 and NANOG were expressed only in CS12 cells. Increased expression of homeobox A13 (HoxA13) and its downstream cascades was significant for the tumorigenic activity of CS12 cells, and was associated with recruitment of E2F-1 to HoxA13 promoter accompanied with increased trimethylation of histone H3 lysine 4 (H3K4me3) at the hypomethylated E2F motifs. Knockdown of HoxA13 caused the downregulation of long non-coding RNA HOTTIP and insulin growth factor-binding protein 3 (IGFBP-3) genes, indicating that both were targets of HoxA13. Concurrent regulation of HoxA13-HOTTIP was mediated by the mixed lineage leukemia-WD repeat domain 5 complex, which caused the trimethylation of H3K4 and then stimulated cell proliferation. HoxA13 transactivated the IGFBP-3 promoter through the HOX-binding site. Activation of IGFBP-3 stimulated the oncogenic potential and invasion activity. Increased expression of HoxA13 (63.2%) and IGFBP-3 (28.6%) was detected in human gastric cancer tissues and was found in the gastric cancer data of The Cancer Genome Atlas. Taken together, the HoxA13–HOTTIP–IGFBP-3 cascade is critical for the carcinogenic characteristics of CS12 cells.

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“…An increased expression level of HOTTIP has been observed in various types of tumor (9)(10)(11)(12)(13)(14). Furthermore, the overexpression of HOTTIP has been previously shown to be significantly correlated with poor prognosis (9)(10)(11)(12)(13)(14). Therefore, HOTTIP may be a candidate to serve as a feasible prognostic factor.…”

Section: Introductionmentioning

confidence: 99%

Long non‑coding RNA HOTTIP is able to predict poor prognosis in various neoplasms: A meta‑analysis

Jin

Yang

2017

mol clin onc

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Abstract. HOXA distal transcript antisense RNA (HOTTIP), a critical oncogenic long non-coding RNA, has been reported to be aberrantly regulated in various cancer types. The present meta-analysis aimed to investigate HOTTIP as a potential clinical applicable prognostic biomarker in malignant neoplasms. Literature collections were performed by searching the electronic databases, PubMed and Web of Science (up to July 20, 2016). All the relevant searches were conducted to identify the association of HOTTIP with the overall survival (OS) rate. A total of six articles consisting of 508 patients were included in the present meta-analysis. The results suggested that the overexpression of HOTTIP is closely correlated with poor OS (hazard ratio=2.28; 95% confidence interval=1.71-3.04; P=0.000). In conclusion, the present meta-analysis has demonstrated that an increased expression level of HOTTIP is correlated with poor OS in different types of cancer, suggesting that HOTTIP potentially serves as a reliable prognostic biomarker in different types of cancer.

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Long non-coding RNA HOTTIP is correlated with progression and prognosis in tongue squamous cell carcinoma

Cited by 87 publications

References 27 publications

The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

The prognostic value of long noncoding RNA HOTTIP on clinical outcomes in breast cancer

Oncogenic function of the homeobox A13-long noncoding RNA HOTTIP-insulin growth factor-binding protein 3 axis in human gastric cancer

Long non‑coding RNA HOTTIP is able to predict poor prognosis in various neoplasms: A meta‑analysis

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