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The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma.

Wu Y, Liu H, Shi X, Yao Y, Yang W, Song Y - Oncotarget (2015)

Bottom Line: The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup.In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin.In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

ABSTRACT
Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and β-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.

No MeSH data available.


Related in: MedlinePlus

Effects of HNF1A-AS1 downexpression on tumor metastasis in vitro and in vivo(A, B, C) and (D) Transwell assays were performed to determine the migratory and invasive abilities of si-HNF1A-AS1-transfected A549 and SPC-A1 cells. (E) and (F) Analysis of an experimental metastasis animal model was performed by injecting HNF1A-AS1 knockdown A549 cells into nude mice. Lungs from mice in each experimental group, with the numbers of tumor nodules on lung surfaces were shown. (G) Visualization of the HE-stained lung sections. **p < 0.01.
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Figure 5: Effects of HNF1A-AS1 downexpression on tumor metastasis in vitro and in vivo(A, B, C) and (D) Transwell assays were performed to determine the migratory and invasive abilities of si-HNF1A-AS1-transfected A549 and SPC-A1 cells. (E) and (F) Analysis of an experimental metastasis animal model was performed by injecting HNF1A-AS1 knockdown A549 cells into nude mice. Lungs from mice in each experimental group, with the numbers of tumor nodules on lung surfaces were shown. (G) Visualization of the HE-stained lung sections. **p < 0.01.

Mentions: To determine whether the inhibition of HNF1A-AS1 expression can promote NSCLC migration and invasion, we evaluated cancer cell invasion through Matrigel and migration through Transwells. Decreased HNF1A-AS1 expression impeded A549 cell migration by 61% and 49% when knocked down by siRNA1 and siRNA2, respectively (Figure 5A and 5B), and by 61% and 43% in SPC-A1 (Figure 5C and 5D). Similarly, A549 cell invasion was also reduced by 45% and 21% by siRNA1 and siRNA2, respectively (Figure 5A and 5B). Down-regulation of HNF1A-AS1 expression also impaired the invasion of SPC-A1 by 34% and 23% by siRNA1 and siRNA2 (Figure 5C and 5D). These findings support the conclusion that HNF1A-AS1 exerts a critical effect on the promotion of lung adenocarcinoma cell migration and invasion.


The long non-coding RNA HNF1A-AS1 regulates proliferation and metastasis in lung adenocarcinoma.

Wu Y, Liu H, Shi X, Yao Y, Yang W, Song Y - Oncotarget (2015)

Effects of HNF1A-AS1 downexpression on tumor metastasis in vitro and in vivo(A, B, C) and (D) Transwell assays were performed to determine the migratory and invasive abilities of si-HNF1A-AS1-transfected A549 and SPC-A1 cells. (E) and (F) Analysis of an experimental metastasis animal model was performed by injecting HNF1A-AS1 knockdown A549 cells into nude mice. Lungs from mice in each experimental group, with the numbers of tumor nodules on lung surfaces were shown. (G) Visualization of the HE-stained lung sections. **p < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496209&req=5

Figure 5: Effects of HNF1A-AS1 downexpression on tumor metastasis in vitro and in vivo(A, B, C) and (D) Transwell assays were performed to determine the migratory and invasive abilities of si-HNF1A-AS1-transfected A549 and SPC-A1 cells. (E) and (F) Analysis of an experimental metastasis animal model was performed by injecting HNF1A-AS1 knockdown A549 cells into nude mice. Lungs from mice in each experimental group, with the numbers of tumor nodules on lung surfaces were shown. (G) Visualization of the HE-stained lung sections. **p < 0.01.
Mentions: To determine whether the inhibition of HNF1A-AS1 expression can promote NSCLC migration and invasion, we evaluated cancer cell invasion through Matrigel and migration through Transwells. Decreased HNF1A-AS1 expression impeded A549 cell migration by 61% and 49% when knocked down by siRNA1 and siRNA2, respectively (Figure 5A and 5B), and by 61% and 43% in SPC-A1 (Figure 5C and 5D). Similarly, A549 cell invasion was also reduced by 45% and 21% by siRNA1 and siRNA2, respectively (Figure 5A and 5B). Down-regulation of HNF1A-AS1 expression also impaired the invasion of SPC-A1 by 34% and 23% by siRNA1 and siRNA2 (Figure 5C and 5D). These findings support the conclusion that HNF1A-AS1 exerts a critical effect on the promotion of lung adenocarcinoma cell migration and invasion.

Bottom Line: The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup.In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin.In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

ABSTRACT
Long noncoding RNAs (lncRNAs) have emerged as key regulators of tumor development and progression. The lncRNA HNF1A-antisense 1 (HNF1A-AS1) is a 2455-bp transcript on chromosome 12 with a potential oncogenic role in esophageal adenocarcinoma. Nevertheless, current understanding of the involvement of HNF1A-AS1 in lung adenocarcinoma tumorigenesis remains limited. In this study, we analyzed the roles of HNF1A-AS1 in 40 lung adenocarcinoma tissues and five lung cancer cell lines. Our results showed that HNF1A-AS1 was significantly up-regulated in lung adenocarcinoma tissues compared with corresponding non-tumor tissues, and its expression level was significantly correlated with TNM stage, tumor size, and lymph node metastasis. The UCSC Cancer Genomics Browser's Kaplan-Meier plot suggested that patients in the high HNF1A-AS1 expression subgroup experienced worse overall survival compared to the low expression subgroup. Moreover, HNF1A-AS1 was determined to promote tumor proliferation and metastasis, both in vitro and in vivo, by regulating cyclin D1, E-cadherin, N-cadherin and β-catenin expression. In addition, the binding of HNF1A-AS1 to DNMT1 may explain its regulation of E-cadherin. In conclusions, we demonstrated that increased HNF1A-AS1 expression could regulate cell proliferation and metastasis and identified it as a poor prognostic biomarker in lung adenocarcinoma.

No MeSH data available.


Related in: MedlinePlus