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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

Relative HNF1A-AS1 expression in lung adenocarcinoma tissues and its clinical significance(A) Relative expression of HNF1A-AS1 expression in lung adenocarcinoma tissues (n = 40) and in paired adjacent normal tissues (n = 40). HNF1A-AS1 expression was examined by qPCR and normalized to GAPDH expression. (shown as ΔCT) (B–D) HNF1A-AS1 expression was significantly higher in patients with big tumor size, advanced clinical stage and lymph nodes metastasis. (E) The Kaplan-Meier plot in UCSC Cancer Genomics Browser indicated that HNF1A-AS1 high expression (red line) has a worse overall survival compared to the low expression subgroup (green line). See https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/#? bookmark=3c7d51368bb7caa36d17e4c957103893. *p < 0.05.
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Figure 1: Relative HNF1A-AS1 expression in lung adenocarcinoma tissues and its clinical significance(A) Relative expression of HNF1A-AS1 expression in lung adenocarcinoma tissues (n = 40) and in paired adjacent normal tissues (n = 40). HNF1A-AS1 expression was examined by qPCR and normalized to GAPDH expression. (shown as ΔCT) (B–D) HNF1A-AS1 expression was significantly higher in patients with big tumor size, advanced clinical stage and lymph nodes metastasis. (E) The Kaplan-Meier plot in UCSC Cancer Genomics Browser indicated that HNF1A-AS1 high expression (red line) has a worse overall survival compared to the low expression subgroup (green line). See https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/#? bookmark=3c7d51368bb7caa36d17e4c957103893. *p < 0.05.

Mentions: To validate whether HNF1A-AS1 was differentially expressed in lung adenocarcinoma tissues, a total of 40 paired clinical lung adenocarcinoma tissues and adjacent normal counterparts were analyzed for HNF1A-AS1 expression using qRT-PCR. HNF1A-AS1 expression was significantly over-regulated in cancerous tissues (p = 0.03; Figure 1A). In addition, to evaluate the clinical significance of HNF1A-AS1, we assessed the correlation of its expression with clinicopathological parameters (i.e., stage, maximum diameter and lymph node metastasis). As shown in Figure 1B, 1C, 1D and Table 1, HNF1A-AS1 expression levels in lung adenocarcinoma were significantly associated with tumor size (p = 0.022), TNM stage (p = 0.046), and lymph node metastasis (p = 0.011). However, HNF1A-AS1 expression was not correlated with other clinical characteristics such as differentiation (p = 0.354), gender (p = 0.722) or age (p = 0.505) in lung adenocarcinoma (Table 1).


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)

Relative HNF1A-AS1 expression in lung adenocarcinoma tissues and its clinical significance(A) Relative expression of HNF1A-AS1 expression in lung adenocarcinoma tissues (n = 40) and in paired adjacent normal tissues (n = 40). HNF1A-AS1 expression was examined by qPCR and normalized to GAPDH expression. (shown as ΔCT) (B–D) HNF1A-AS1 expression was significantly higher in patients with big tumor size, advanced clinical stage and lymph nodes metastasis. (E) The Kaplan-Meier plot in UCSC Cancer Genomics Browser indicated that HNF1A-AS1 high expression (red line) has a worse overall survival compared to the low expression subgroup (green line). See https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/#? bookmark=3c7d51368bb7caa36d17e4c957103893. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Relative HNF1A-AS1 expression in lung adenocarcinoma tissues and its clinical significance(A) Relative expression of HNF1A-AS1 expression in lung adenocarcinoma tissues (n = 40) and in paired adjacent normal tissues (n = 40). HNF1A-AS1 expression was examined by qPCR and normalized to GAPDH expression. (shown as ΔCT) (B–D) HNF1A-AS1 expression was significantly higher in patients with big tumor size, advanced clinical stage and lymph nodes metastasis. (E) The Kaplan-Meier plot in UCSC Cancer Genomics Browser indicated that HNF1A-AS1 high expression (red line) has a worse overall survival compared to the low expression subgroup (green line). See https://genome-cancer.ucsc.edu/proj/site/hgHeatmap/#? bookmark=3c7d51368bb7caa36d17e4c957103893. *p < 0.05.
Mentions: To validate whether HNF1A-AS1 was differentially expressed in lung adenocarcinoma tissues, a total of 40 paired clinical lung adenocarcinoma tissues and adjacent normal counterparts were analyzed for HNF1A-AS1 expression using qRT-PCR. HNF1A-AS1 expression was significantly over-regulated in cancerous tissues (p = 0.03; Figure 1A). In addition, to evaluate the clinical significance of HNF1A-AS1, we assessed the correlation of its expression with clinicopathological parameters (i.e., stage, maximum diameter and lymph node metastasis). As shown in Figure 1B, 1C, 1D and Table 1, HNF1A-AS1 expression levels in lung adenocarcinoma were significantly associated with tumor size (p = 0.022), TNM stage (p = 0.046), and lymph node metastasis (p = 0.011). However, HNF1A-AS1 expression was not correlated with other clinical characteristics such as differentiation (p = 0.354), gender (p = 0.722) or age (p = 0.505) in lung adenocarcinoma (Table 1).

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