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Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway.

Wang F, Ying HQ, He BS, Pan YQ, Deng QW, Sun HL, Chen J, Liu X, Wang SK - Oncotarget (2015)

Bottom Line: The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers.Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC.Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

View Article: PubMed Central - PubMed

Affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

No MeSH data available.


Related in: MedlinePlus

Relative UCA1 expression in HCC tissues and its relationship with overall survival of HCC patients(A) Unsupervised hierarchical clustering analysis on the most 20 significantly dysregulated lncRNAs resulted from microarray assay. The normalized expression values are represented in shades of red and green, indicating expression above and below the median expression value across all of the samples. (B) UCA1 expression was examined by qRT-PCR and normalized to GAPDH expression in 98 pairs of HCC tissues (T) compared with corresponding nontumourous liver specimens (N), **P < 0.001. (C) Semiquantitative RT-PCR analysis of UCA1 expression from 5 patients with HCC; T, tumor tissues; N, corresponding adjacent normal tissues. (D) Kaplan-Meier survival curve and log-rank test were used to evaluate whether UCA1 expression level was associated with overall survival rate. Patients were segregated into UCA1-high group and UCA1-low according to the median of UCA1 expression in HCC.
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Figure 1: Relative UCA1 expression in HCC tissues and its relationship with overall survival of HCC patients(A) Unsupervised hierarchical clustering analysis on the most 20 significantly dysregulated lncRNAs resulted from microarray assay. The normalized expression values are represented in shades of red and green, indicating expression above and below the median expression value across all of the samples. (B) UCA1 expression was examined by qRT-PCR and normalized to GAPDH expression in 98 pairs of HCC tissues (T) compared with corresponding nontumourous liver specimens (N), **P < 0.001. (C) Semiquantitative RT-PCR analysis of UCA1 expression from 5 patients with HCC; T, tumor tissues; N, corresponding adjacent normal tissues. (D) Kaplan-Meier survival curve and log-rank test were used to evaluate whether UCA1 expression level was associated with overall survival rate. Patients were segregated into UCA1-high group and UCA1-low according to the median of UCA1 expression in HCC.

Mentions: Firstly, the Agilent G3 Human GE Microarray (8 × 60 K) was used to analyze lncRNA expression profiles in 4 HCC tissues and paired corresponding nontumourous tissues. Fold change greater than 2 and P value less than 0.05 between tumor tissues and adjacent normal tissues were set as the criteria in filtering differently expressed lncRNAs. Results of unsupervised hierarchical clustering analysis on the top 20 significantly dysregulated lncRNAs were shown in Figure 1A. We further analyzed the expression of the top 20 upregulated lncRNAs in HCC tissues by qRT-PCR and finally focused on UCA1 in our study.


Upregulated lncRNA-UCA1 contributes to progression of hepatocellular carcinoma through inhibition of miR-216b and activation of FGFR1/ERK signaling pathway.

Wang F, Ying HQ, He BS, Pan YQ, Deng QW, Sun HL, Chen J, Liu X, Wang SK - Oncotarget (2015)

Relative UCA1 expression in HCC tissues and its relationship with overall survival of HCC patients(A) Unsupervised hierarchical clustering analysis on the most 20 significantly dysregulated lncRNAs resulted from microarray assay. The normalized expression values are represented in shades of red and green, indicating expression above and below the median expression value across all of the samples. (B) UCA1 expression was examined by qRT-PCR and normalized to GAPDH expression in 98 pairs of HCC tissues (T) compared with corresponding nontumourous liver specimens (N), **P < 0.001. (C) Semiquantitative RT-PCR analysis of UCA1 expression from 5 patients with HCC; T, tumor tissues; N, corresponding adjacent normal tissues. (D) Kaplan-Meier survival curve and log-rank test were used to evaluate whether UCA1 expression level was associated with overall survival rate. Patients were segregated into UCA1-high group and UCA1-low according to the median of UCA1 expression in HCC.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480724&req=5

Figure 1: Relative UCA1 expression in HCC tissues and its relationship with overall survival of HCC patients(A) Unsupervised hierarchical clustering analysis on the most 20 significantly dysregulated lncRNAs resulted from microarray assay. The normalized expression values are represented in shades of red and green, indicating expression above and below the median expression value across all of the samples. (B) UCA1 expression was examined by qRT-PCR and normalized to GAPDH expression in 98 pairs of HCC tissues (T) compared with corresponding nontumourous liver specimens (N), **P < 0.001. (C) Semiquantitative RT-PCR analysis of UCA1 expression from 5 patients with HCC; T, tumor tissues; N, corresponding adjacent normal tissues. (D) Kaplan-Meier survival curve and log-rank test were used to evaluate whether UCA1 expression level was associated with overall survival rate. Patients were segregated into UCA1-high group and UCA1-low according to the median of UCA1 expression in HCC.
Mentions: Firstly, the Agilent G3 Human GE Microarray (8 × 60 K) was used to analyze lncRNA expression profiles in 4 HCC tissues and paired corresponding nontumourous tissues. Fold change greater than 2 and P value less than 0.05 between tumor tissues and adjacent normal tissues were set as the criteria in filtering differently expressed lncRNAs. Results of unsupervised hierarchical clustering analysis on the top 20 significantly dysregulated lncRNAs were shown in Figure 1A. We further analyzed the expression of the top 20 upregulated lncRNAs in HCC tissues by qRT-PCR and finally focused on UCA1 in our study.

Bottom Line: The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers.Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC.Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

View Article: PubMed Central - PubMed

Affiliation: Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

ABSTRACT
The long non-coding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated, which plays an important role in the progression of several cancers. However, the biological role and clinical significance of UCA1 in the carcinogenesis of hepatocellular carcinoma (HCC) remain unclear. Herein, we found that UCA1 was aberrantly upregulated in HCC tissues and associated with TNM stage, metastasis and postoperative survival. UCA1 depletion inhibited the growth and metastasis of HCC cell lines in vitro and in vivo. Furthermore, UCA1 could act as an endogenous sponge by directly binding to miR-216b and downregulation miR-216b expression. In addition, UCA1 could reverse the inhibitory effect of miR-216b on the growth and metastasis of HCC cells, which might be involved in the derepression of fibroblast growth factor receptor 1 (FGFR1) expression, a target gene of miR-216b, and the activation of ERK signaling pathway. Taken together, our data highlights the pivotal role of UCA1 in the tumorigenesis of HCC. Moreover, the present study elucidates a novel lncRNA-miRNA-mRNA regulatory network that is UCA1-miR-216b-FGFR1-ERK signaling pathway in HCC, which may help to lead a better understanding the pathogenesis of HCC and probe the feasibility of lncRNA-directed diagnosis and therapy for this deadly disease.

No MeSH data available.


Related in: MedlinePlus