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Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression

View Article: PubMed Central - PubMed

ABSTRACT

Background: Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis. This study was conducted to explore the effect of microRNAs on HCC metastasis.

Methods: The levels of miR-181a in HCC tissues, adjacent tissues, metastatic HCC tissues, and non-metastatic HCC tissues at different stages were determined by qRT-PCR. Effect of miR-181a on the proliferation, invasion, and metastasis of HCC cells was estimated by cell counting kits-8 (CCK-8), wound-healing, and Transwell assays. Software analysis and luciferase assays were used to explore the target gene of miR-181a.

Results: MiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST. The regulation of miR-181a on PTEN was mediated by lncRNA XIST. The proliferation and invasion of cells with siXIST were significantly enhanced compared with those of control cells, while knockdown of miR-181a abolished the enhancing effects.

Conclusions: MiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.

Electronic supplementary material: The online version of this article (doi:10.1186/s12885-017-3216-6) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus

Expression levels of miR-181a in HCC tissues and plasma samples. a Partial miRNAs expression profiles of HCC tissues. b Relative expression level of miR-181a in HCC tissues and normal liver tissues. c Relative expression level of miR-181a in HCC metastatic and non-metastatic tissues. d Relative expression level of miR-181a in different TNM stage. e Relative expression level of miR-181a in serum of HCC patients and normal. f The positive correlation between AFP and miR-181a levels in the plasma of HCC patients. HCC, hepatocellular carcinoma
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Fig1: Expression levels of miR-181a in HCC tissues and plasma samples. a Partial miRNAs expression profiles of HCC tissues. b Relative expression level of miR-181a in HCC tissues and normal liver tissues. c Relative expression level of miR-181a in HCC metastatic and non-metastatic tissues. d Relative expression level of miR-181a in different TNM stage. e Relative expression level of miR-181a in serum of HCC patients and normal. f The positive correlation between AFP and miR-181a levels in the plasma of HCC patients. HCC, hepatocellular carcinoma

Mentions: To explore whether and how miRNAs play key roles in HCC, miRNA data were downloaded from the database and uploaded to GEO (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77314) to screen differentially expressed genes. Results showed 16 miRNAs were down-regulated and 34 miRNAs were up-regulated (Fig. 1a). Among the 34 up-regulated miRNAs, the degree of up-regulation of miR-181a was the most marked. To explore the influence of miR-181a on HCC, 55 HCC tissue samples and the adjacent normal tissues were selected. The relative mRNA level of miR-181a in them was determined and compared. Results showed the level of miR-181a in HCC tissues was significantly higher than that in the adjacent tissues (Fig. 1b). To study the relationship between miR-181a and tumor metastasis, we studied the level of miR-181a in the invasive and normal tissues. Results showed the miR-181a expression levels in metastatic HCC tissues were dramatically higher than those in non-metastatic HCC tissues (Fig. 1c). Moreover, the levels of miR-181a in HCC tissues at different stages were also determined by qRT-PCR. Results showed the level of miR-181a in stage III and IV was markedly higher than that during stage I and II (Fig. 1d). It indicated miR-181a may be closely related to the TNM stage of HCC. Then the level of miR-181a in serum of HCC patients was determined and compared with normal levels. The results showed that the miR-181a level in HCC serum was significantly higher than normal (Fig. 1e). Moreover, the level of miR-181a was positively related with alpha feto protein (AFP) (Fig. 1f). AFP is a fetal glycoprotein produced by the yolk sac and fetal liver. It was reported to have a role in diagnosing and managing HCC [13]. These results indicated miR-181a is a potential biomarker to aid in HCC detection.Fig. 1


Long non-coding RNA XIST regulates PTEN expression by sponging miR-181a and promotes hepatocellular carcinoma progression
Expression levels of miR-181a in HCC tissues and plasma samples. a Partial miRNAs expression profiles of HCC tissues. b Relative expression level of miR-181a in HCC tissues and normal liver tissues. c Relative expression level of miR-181a in HCC metastatic and non-metastatic tissues. d Relative expression level of miR-181a in different TNM stage. e Relative expression level of miR-181a in serum of HCC patients and normal. f The positive correlation between AFP and miR-181a levels in the plasma of HCC patients. HCC, hepatocellular carcinoma
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5383949&req=5

Fig1: Expression levels of miR-181a in HCC tissues and plasma samples. a Partial miRNAs expression profiles of HCC tissues. b Relative expression level of miR-181a in HCC tissues and normal liver tissues. c Relative expression level of miR-181a in HCC metastatic and non-metastatic tissues. d Relative expression level of miR-181a in different TNM stage. e Relative expression level of miR-181a in serum of HCC patients and normal. f The positive correlation between AFP and miR-181a levels in the plasma of HCC patients. HCC, hepatocellular carcinoma
Mentions: To explore whether and how miRNAs play key roles in HCC, miRNA data were downloaded from the database and uploaded to GEO (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77314) to screen differentially expressed genes. Results showed 16 miRNAs were down-regulated and 34 miRNAs were up-regulated (Fig. 1a). Among the 34 up-regulated miRNAs, the degree of up-regulation of miR-181a was the most marked. To explore the influence of miR-181a on HCC, 55 HCC tissue samples and the adjacent normal tissues were selected. The relative mRNA level of miR-181a in them was determined and compared. Results showed the level of miR-181a in HCC tissues was significantly higher than that in the adjacent tissues (Fig. 1b). To study the relationship between miR-181a and tumor metastasis, we studied the level of miR-181a in the invasive and normal tissues. Results showed the miR-181a expression levels in metastatic HCC tissues were dramatically higher than those in non-metastatic HCC tissues (Fig. 1c). Moreover, the levels of miR-181a in HCC tissues at different stages were also determined by qRT-PCR. Results showed the level of miR-181a in stage III and IV was markedly higher than that during stage I and II (Fig. 1d). It indicated miR-181a may be closely related to the TNM stage of HCC. Then the level of miR-181a in serum of HCC patients was determined and compared with normal levels. The results showed that the miR-181a level in HCC serum was significantly higher than normal (Fig. 1e). Moreover, the level of miR-181a was positively related with alpha feto protein (AFP) (Fig. 1f). AFP is a fetal glycoprotein produced by the yolk sac and fetal liver. It was reported to have a role in diagnosing and managing HCC [13]. These results indicated miR-181a is a potential biomarker to aid in HCC detection.Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

Background: Tumor metastasis often occurs in hepatocellular carcinoma (HCC) and influences the patient’s prognosis, and microRNAs are reported to play key roles in tumor metastasis. This study was conducted to explore the effect of microRNAs on HCC metastasis.

Methods: The levels of miR-181a in HCC tissues, adjacent tissues, metastatic HCC tissues, and non-metastatic HCC tissues at different stages were determined by qRT-PCR. Effect of miR-181a on the proliferation, invasion, and metastasis of HCC cells was estimated by cell counting kits-8 (CCK-8), wound-healing, and Transwell assays. Software analysis and luciferase assays were used to explore the target gene of miR-181a.

Results: MiR-181a was up-regulated in HCC tissues and its expression level in metastatic HCC tissues was much higher than in non-metastasis samples. PTEN was found to be a target gene of miR-181a. MiR-181a had multiple binding sites with the long non-coding RNA (lncRNA) XIST. The regulation of miR-181a on PTEN was mediated by lncRNA XIST. The proliferation and invasion of cells with siXIST were significantly enhanced compared with those of control cells, while knockdown of miR-181a abolished the enhancing effects.

Conclusions: MiR-181a can promote HCC metastasis by targeting PTEN, which is regulated by lncRNA XIST.

Electronic supplementary material: The online version of this article (doi:10.1186/s12885-017-3216-6) contains supplementary material, which is available to authorized users.

No MeSH data available.


Related in: MedlinePlus