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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

UCA1-knockdown suppresses cell proliferation, colony formation, cell migration, invasion and induces cell cycle arrest of HCC cells(A) UCA1 expression levels were analyzed in different liver cell lines by qRT-PCR and GAPDH was treated as internal control. (B) UCA1 expression was examined in NC (non-transfected control), siRNA-NC (siRNA non-targeting control) and siUCA1 (siRNA-UCA1) transfected SMMC7721 and HepG2 cells by qRT-PCR. GAPDH was used as an internal control. (C) Cell growth viability was assayed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells by CCK-8 at 0 h, 24 h, 48 h and 72 h time point. (D) Colony formation assays were performed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells (left panel, crystal violet staining; right panel, number of colonies from three independent experiments). (E) Cell cycle profile was examined by flow cytometry with propidium iodide staining, cell number were counted according to DNA content of G0/G1, S and G2/M phases (left panel). The statistical results were shown on the right panel. Representative images of migration (F) and invasion (G) of SMMC7721 and HepG2 cells transfected with siUCA1 and siRNA-NC were showed on the left panel (200 × magnification). The number of migrated and invaded cells was measured in the right panel, respectively, mean ± SD, *P < 0.05, **P < 0.01.
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Figure 2: UCA1-knockdown suppresses cell proliferation, colony formation, cell migration, invasion and induces cell cycle arrest of HCC cells(A) UCA1 expression levels were analyzed in different liver cell lines by qRT-PCR and GAPDH was treated as internal control. (B) UCA1 expression was examined in NC (non-transfected control), siRNA-NC (siRNA non-targeting control) and siUCA1 (siRNA-UCA1) transfected SMMC7721 and HepG2 cells by qRT-PCR. GAPDH was used as an internal control. (C) Cell growth viability was assayed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells by CCK-8 at 0 h, 24 h, 48 h and 72 h time point. (D) Colony formation assays were performed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells (left panel, crystal violet staining; right panel, number of colonies from three independent experiments). (E) Cell cycle profile was examined by flow cytometry with propidium iodide staining, cell number were counted according to DNA content of G0/G1, S and G2/M phases (left panel). The statistical results were shown on the right panel. Representative images of migration (F) and invasion (G) of SMMC7721 and HepG2 cells transfected with siUCA1 and siRNA-NC were showed on the left panel (200 × magnification). The number of migrated and invaded cells was measured in the right panel, respectively, mean ± SD, *P < 0.05, **P < 0.01.

Mentions: Based on above observations, an analysis of UCA1 expression was carried out among 5 different HCC cell lines (MHCC97L, SMMC7721, MHCC97H, HepG2 and SK-Hep1) and a normal liver cell line (HL-7702). We noted that UCA1 was obviously overexpressed in 5 HCC cell lines than that of HL-7702 cells, especially in SMMC7721 and HepG2 cell lines (Figure 2A). Thus, SMMC7721 and HepG2 cell lines were selected as research represents of HCC cells in the following studies.


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)

UCA1-knockdown suppresses cell proliferation, colony formation, cell migration, invasion and induces cell cycle arrest of HCC cells(A) UCA1 expression levels were analyzed in different liver cell lines by qRT-PCR and GAPDH was treated as internal control. (B) UCA1 expression was examined in NC (non-transfected control), siRNA-NC (siRNA non-targeting control) and siUCA1 (siRNA-UCA1) transfected SMMC7721 and HepG2 cells by qRT-PCR. GAPDH was used as an internal control. (C) Cell growth viability was assayed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells by CCK-8 at 0 h, 24 h, 48 h and 72 h time point. (D) Colony formation assays were performed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells (left panel, crystal violet staining; right panel, number of colonies from three independent experiments). (E) Cell cycle profile was examined by flow cytometry with propidium iodide staining, cell number were counted according to DNA content of G0/G1, S and G2/M phases (left panel). The statistical results were shown on the right panel. Representative images of migration (F) and invasion (G) of SMMC7721 and HepG2 cells transfected with siUCA1 and siRNA-NC were showed on the left panel (200 × magnification). The number of migrated and invaded cells was measured in the right panel, respectively, mean ± SD, *P < 0.05, **P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: UCA1-knockdown suppresses cell proliferation, colony formation, cell migration, invasion and induces cell cycle arrest of HCC cells(A) UCA1 expression levels were analyzed in different liver cell lines by qRT-PCR and GAPDH was treated as internal control. (B) UCA1 expression was examined in NC (non-transfected control), siRNA-NC (siRNA non-targeting control) and siUCA1 (siRNA-UCA1) transfected SMMC7721 and HepG2 cells by qRT-PCR. GAPDH was used as an internal control. (C) Cell growth viability was assayed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells by CCK-8 at 0 h, 24 h, 48 h and 72 h time point. (D) Colony formation assays were performed in NC, siRNA-NC and siUCA1 transfected SMMC7721 and HepG2 cells (left panel, crystal violet staining; right panel, number of colonies from three independent experiments). (E) Cell cycle profile was examined by flow cytometry with propidium iodide staining, cell number were counted according to DNA content of G0/G1, S and G2/M phases (left panel). The statistical results were shown on the right panel. Representative images of migration (F) and invasion (G) of SMMC7721 and HepG2 cells transfected with siUCA1 and siRNA-NC were showed on the left panel (200 × magnification). The number of migrated and invaded cells was measured in the right panel, respectively, mean ± SD, *P < 0.05, **P < 0.01.
Mentions: Based on above observations, an analysis of UCA1 expression was carried out among 5 different HCC cell lines (MHCC97L, SMMC7721, MHCC97H, HepG2 and SK-Hep1) and a normal liver cell line (HL-7702). We noted that UCA1 was obviously overexpressed in 5 HCC cell lines than that of HL-7702 cells, especially in SMMC7721 and HepG2 cell lines (Figure 2A). Thus, SMMC7721 and HepG2 cell lines were selected as research represents of HCC cells in the following studies.

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