Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer

Huang, Long; Ling, Liming; Liu, An Wen; Wu, Jian; Cheng, Xiao; Ji, Lin; Zheng, Min

doi:10.1007/s00404-014-3236-2

Cited by 141 publications

(136 citation statements)

References 20 publications

Supporting

Mentioning

129

Contrasting

Order By: Relevance

“…This RNA arises from the transcription of the antisense strand of the HOXC gene, which is specifically situated between HOXC11 and HOXC12 on chromosome 12q13.13 (25). HOTAIR is an oncogenic factor and can be used as a prognostic biomarker in different cancer types, since HOTAIR plays a key role in the initiation and progression of different types of cancer, including cervical cancer and nasopharyngeal carcinoma (26). HOTAIR, a lncRNA initially identified in breast cancer, was demonstrated to be upregulated in a variety of carcinomas (27,28).…”

Section: Discussionmentioning

confidence: 99%

HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

Chen

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

Abstract.Evidence is rapidly accumulating that long non-coding RNAs (lncRNAs) are involved in human tumorigenesis and are dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). lncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs may be valuable biomarkers and therapeutic targets. HOX transcript antisense intergenic RNA (HOTAIR) has previously been demonstrated to be an oncogene and a negative prognostic factor in a variety of cancers; however, the factors that contribute to the upregulation of HOTAIR and the interaction between HOTAIR and microRNAs (miRNAs or miRs) are largely unknown. In the present study, the expression levels of HOTAIR, forkhead box C1 (FOXC1) and miRNA-1 were examined in 50 matched pairs of HCC and HCC cells. The effects of HOTAIR on HCC cell proliferation were tested using trypan blue exclusion assay. The effect of HOTAIR on HCC growth in vivo was determined in a (nu/nu) mouse model. A computational screening of HOTAIR promoter was conducted to search for transcription factor-binding sites. FOXC1 binding to the promoter region of HOTAIR was confirmed using a chromatin immunoprecipitation assay. A search for miRNAs that had complementary base paring with HOTAIR was performed utilizing an online software program.The interaction between miR-1 and HOTAIR was examined using a luciferase reporter assay. Gain and loss of function approaches were used to determine the changes of HOTAIR or miR-1 expression. The relative levels of FOXC1 and HOTAIR expression in HCC tissues and HepG2 cells were significantly higher than those in normal liver LO2 cells and adjacent carcinoma tissues; the relative expression of miR-1 exhibited the opposite pattern. Overexpression of HOTAIR promoted HCC cell proliferation and progression of tumor xenografts. The present authors have demonstrated that FOXC1 binds to the upstream region of HOTAIR in HCC cells and that FOXC1 activates lncRNA HOTAIR expression in HCC HepG2 cells, which suggests that HOTAIR harbors a miRNA-1 binding site. The present data revealed that this binding site is vital for the regulation of miRNA-1 by HOTAIR. Furthermore, HOTAIR negatively regulated the expression of miRNA-1 in HepG2 cells. Additionally, the present study demonstrated that the oncogenic activity of HOTAIR is in part based on the negative regulation of miR-1. Taken together, these results suggest that HOTAIR is a FOXC1-activated driver of malignancy, which acts in part through the repression of miR-1. IntroductionHepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortalities, with nearly 600,000 mortalities occurring worldwide each year (1). Although resection is considered a potentially curative treatment for HCC patients, the 1-year post-operative survival rate is only 30-40% (2). Thus, it is necessary to improve our understanding of the disease-causing mechanisms and to identify specific biomarkers for HCC progression to aid in the predictio...

show abstract

Section: Discussionmentioning

confidence: 99%

HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

Chen

et al. 2016

Oncology Letters

View full text Add to dashboard Cite

show abstract

“…For instance, MALAT1 expression is increased in colorectal cancer and pancreatic duct adenocarcinoma tissues, having been predicated as a biomarker for prognosis and metastasis in these diseases . High expression of lncRNA HOTAIR is strongly associated with clinical characteristics in cervical cancer including FIGO stage, lymph node metastasis, invasion depth, and tumor size (Huang et al 2014). Pancreatic cancer patients of the high-lncRNA-PVT1 group had obviously shorter overall survival times than those of the low-expression group .…”

Section: Introductionmentioning

confidence: 97%

Elevated Expression Levels of Long Non-Coding RNA, Loc554202, Are Predictive of Poor Prognosis in Cervical Cancer

Chen

Zhu

2017

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Cervical cancer remains one of the most common causes of gynecological cancer-associated death. Long non-coding RNA Loc554202 (lncRNA Loc554202) has been reported to be involved in the development of several types of cancer. However, the role of Loc554202 in cervical cancer remains unclear. In this study, we measured the expression levels of Loc554202 in cervical cancer tissues from 120 patients. The quantitative real-time PCR analysis showed the expression levels of Loc554202 were significantly higher in cervical cancer tissues compared with the adjacent non-tumor tissues. Elevated expression levels of Loc554202 were significantly associated with tumor size (p = 0.006), FIGO stage (p = 0.015), HPV (p = 0.001), and lymph node metastasis (p = 0.002). Kaplan-Meier analysis clearly illustrated that patients with high expression levels of Loc554202 had a lower overall survival rate compared to patients with lower expression (p = 0.0013). Furthermore, we show that Loc554202 is an independent poor prognostic factor through multivariate analysis. Subsequently, using cervical cancer cell lines, HeLa and ME-180, we decreased the expression levels of Loc554202 with siRNA. As results, the proliferation ability of cervical cancer cells was inhibited and apoptosis was induced after Loc554202 knockdown, as judged by viability assay, colony formation, and flow cytometry. Moreover, knockdown of Loc554202 expression downregulated Bcl-2 expression and conversely up-regulated Bax expression in cervical cancer cells using Western blotting analysis. In conclusion, elevated levels of Loc554202 are predictive of poor prognosis in cervical cancer. We suggest that Loc554202 may serve as a potential therapeutic target for cervical cancer.

show abstract

“…The lncRNA expression profiling data showed that there were lncRNAs that were differentially expressed between the PDAC tissues and matched adjacent non-tumor tissues. Previous studies showed that dysregulation of lncRNAs expression such as HOTAIR (32,33), HULC (34)(35)(36) and GAS5 (37,38), is a potential molecular marker for diagnostic and therapeutic purposes in several human cancers. There are still lncRNAs as potential novel candidate molecular markers for clinical diagnosis and therapy of PDAC that need to be further identified.…”

Section: Discussionmentioning

confidence: 99%

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

Zhou

Gong

Jiang

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Long non-coding RNA (lncRNA) is a variety of the human transcriptome that does not code for proteins and plays an important role in the development and progression of multiple solid malignant tumors. However, the roles of lncRNAs in the development of pancreatic ductal adenocarcinoma (PDAC) remain unknown. In this study, we investigated the expression patterns of lncRNAs in three PDAC tumor samples (T) relative to those of matched adjacent non-tumor tissues (N) via a microarray with 30,586 lncRNA probes and 26,109 mRNA probes. The lncRNA microarray revealed 27,279 lncRNAs in PDAC samples, of which 2,331 were significantly upregulated (P<0.05; T/N>2.0) and 1,641 were downregulated (P<0.05; N/T>2.0) compared with matched adjacent non-tumor samples. In addition, 19,995 mRNAs were detected, of which 1,676 were significantly upregulated (P<0.05; T/N>2.0) and 1,981 were downregulated (P<0.05; N/T>2.0). Pathway analysis indicated that 41 pathways corresponded to upregulated transcripts and 25 pathways corresponded to downregulated transcripts (P-value cut-off is 0.05). Gene ontology (GO) analysis showed that the highest enriched GOs targeted by upregulated and downregulated transcripts were tissue homeostasis. The validation results from quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and microarray analysis were consistent. Furthermore, the expression level of long intergenic non-coding RNA HOTAIRM1 was upregulated in 12 PDAC tissues samples compared with matched adjacent non-tumor samples by qRT-PCR. The results showed that the lncRNA and mRNA expression profiles differed significantly between the PDAC tissues and their adjacent non-tumor tissues, and the revelation of an association between HOTAIRM1 expression and PDAC is especially noteworthy. These findings may provide new potential molecular markers for diagnosis and treatment of PDAC.

show abstract

Overexpression of long noncoding RNA HOTAIR predicts a poor prognosis in patients with cervical cancer

Abstract: our data indicate that high expression of HOTAIR is involved in cervical cancer progression and could be a potential target for diagnosis and gene therapy.

Cited by 141 publications

References 20 publications

HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

HOTAIR, a long non-coding RNA driver of malignancy whose expression is activated by FOXC1, negatively regulates miRNA-1 in hepatocellular carcinoma

Elevated Expression Levels of Long Non-Coding RNA, Loc554202, Are Predictive of Poor Prognosis in Cervical Cancer

Microarray expression profile analysis of long non-coding RNAs in pancreatic ductal adenocarcinoma

Contact Info

Product

Resources

About