Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer

Qiu, Junjun; Lin, Yingying; Ye, Lechi; Ding, Jianxun; Feng, Weiwei; Jin, Huajun; Zhang, Ying; Li, Qing; Hua, Keqin

doi:10.1016/j.ygyno.2014.03.556

Cited by 205 publications

(184 citation statements)

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“…Gupta et al (21) reported that HOTAIR is highly expressed in metastatic breast cancer and its high expression in primary breast tumors is a significant predictor of subsequent metastasis and mortality (21). In a similar manner, increased HOTAIR expression may also indicate poor prognosis and promote metastasis in non-small cell lung cancer (25), epithelial ovarian cancer (27) and colon cancer (23).…”

Section: Discussionmentioning

confidence: 99%

“…The 3' end of HOTAIR interacts with lysine-specific histone demethylase 1A (22). Furthermore, recent studies have reported that HOTAIR is highly expressed and associated with poor prognosis in a number of types of cancer, including breast cancer, epithelial ovarian cancer, pancreatic cancer, colorectal cancer, non-small-cell lung cancer and endometrial carcinoma (21,(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

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Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Jianzhi

et al. 2016

Oncology Letters

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Abstract. The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi-quantitative RT-PCR was used to detect the expression level of Wnt/β-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and β-catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/β-catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Jianzhi

et al. 2016

Oncology Letters

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“…Studies have highlighted key regulatory roles of lncRNAs in carcinogenesis and have suggested that some lncRNAs may be potential diagnostic and therapeutic targets in the treatment of OC (23,24). For example, evidence shows that MALAT1 is downregulated in breast cancer, and that knockdown of MALAT1 induces the EMT program, via pathways involving phosphatidylinositide-3 kinase (17).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer

Wang

Guo

2017

Experimental and Therapeutic Medicine

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Abstract. Ovarian cancer (OC) is the leading cause of mortality among gynecological malignancies. Although microRNAs are known to have a key regulatory role in OC, the involvement of long non-coding RNAs in the disease is less established. Previous studies have demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a tumor oncogene in many cancers, though its role in OC remains unclear. The present study reported that MALAT1 expression was markedly upregulated in OC, by knockdown of MALAT1 expression in vivo, using RNA interference (RNAi) with small-interfering RNA (siRNA). It was found that MALAT1 expression was positively correlated with the International Federation of Gynecology and Obstetrics stages of OC, tumor histological grade and lymph node metastasis. In addition, the differential MALAT1 levels between a human ovarian epithelial cell line (HOSE) and OC cell lines (ES-2, OVCAR3, SKOV3 and HO8910) were compared in vitro. Notably, MALAT1 was expressed to a high level in OC cells. Furthermore, exogenous knockdown of MALAT1 significantly repressed growth and migration of OC cells, and promoted their apoptosis. Collectively, the current findings suggest that upregulation of MALAT1 in OC may facilitate tumorigenesis and metastasis. Knockdown of MALAT1 expression has potential as a novel target for the diagnosis and therapy of OC.

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“…Moreover, lncRNAs have emerged as players in the cancer paradigm, demonstrating potential roles in both oncogenic and tumor-suppressive pathways (18)(19)(20)(21). Increasing evidence indicates that these transcripts are frequently aberrantly expressed in cancer, and some of them have been implicated in diagnosis and prognosis (22,23). Recent progress suggests that the involvement of lncRNAs in human cancers could be far more prevalent that previously appreciated.…”

Section: Significancementioning

confidence: 99%

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

Pastori

Kapranov

Penas

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Bromodomain and extraterminal (BET) domain proteins have emerged as promising therapeutic targets in glioblastoma and many other cancers. Small molecule inhibitors of BET bromodomain proteins reduce expression of several oncogenes required for Glioblastoma Multiforme (GBM) progression. However, the mechanism through which BET protein inhibition reduces GBM growth is not completely understood. Long noncoding RNAs (lncRNAs) are important epigenetic regulators with critical roles in cancer initiation and malignant progression, but mechanistic insight into their expression and regulation by BET bromodomain inhibitors remains elusive. In this study, we used Helicos single molecule sequencing to comprehensively profile lncRNAs differentially expressed in GBM, and we identified a subset of GBM-specific lncRNAs whose expression is regulated by BET proteins. Treatment of GBM cells with the BET bromdomain inhibitor I-BET151 reduced levels of the tumorpromoting lncRNA HOX transcript antisense RNA (HOTAIR) and restored the expression of several other GBM down-regulated lncRNAs. Conversely, overexpression of HOTAIR in conjunction with I-BET151 treatment abrogates the antiproliferative activity of the BET bromodomain inhibitor. Moreover, chromatin immunoprecipitation analysis demonstrated binding of Bromodomain Containing 4 (BRD4) to the HOTAIR promoter, suggesting that BET proteins can directly regulate lncRNA expression. Our data unravel a previously unappreciated mechanism through which BET proteins control tumor growth of glioblastoma cells and suggest that modulation of lncRNA networks may, in part, mediate the antiproliferative effects of many epigenetic inhibitors currently in clinical trials for cancer and other diseases.glioblastoma | long noncoding RNAs | epigenetics | BRD4 | I-BET151

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Overexpression of long non-coding RNA HOTAIR predicts poor patient prognosis and promotes tumor metastasis in epithelial ovarian cancer

Cited by 205 publications

References 28 publications

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Long non-coding RNA MALAT1 is upregulated and involved in cell proliferation, migration and apoptosis in ovarian cancer

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

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