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PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells.

Zhang T, Huang XH, Dong L, Hu D, Ge C, Zhan YQ, Xu WX, Yu M, Li W, Wang X, Tang L, Li CY, Yang XM - Mol. Cancer (2010)

Bottom Line: We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing.A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues.We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Beijing Institute of Radiation Medicine, Beijing, 100850, China.

ABSTRACT

Background: PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive.

Results: We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing. Invasion assay suggested that PCBP1 played a negative role in tumor invasion and re-expression of v6 partly reversed the inhibition effect by PCBP1. A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues.

Conclusions: We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

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Related in: MedlinePlus

Negative Correlation of PCBP1 and CD44 v6 mRNA expression in HCC tissue samples analyzed. Total RNA was extracted from HCC specimens and their adjacent non-cancerous liver tissues for real-time PCR analysis. The expression levels of PCBP1, v6 and std in non-cancerous tissues were set to 1 and normalized to GAPDH mRNA. The experiments in each sample were performed in triplicate with at least 3 independent times. The data was shown as the average of these experiments. Then Spearman test was performed.
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Figure 5: Negative Correlation of PCBP1 and CD44 v6 mRNA expression in HCC tissue samples analyzed. Total RNA was extracted from HCC specimens and their adjacent non-cancerous liver tissues for real-time PCR analysis. The expression levels of PCBP1, v6 and std in non-cancerous tissues were set to 1 and normalized to GAPDH mRNA. The experiments in each sample were performed in triplicate with at least 3 independent times. The data was shown as the average of these experiments. Then Spearman test was performed.

Mentions: Since PCBP1 was a negative regulator of CD44 v6 expression and tumor invasion, we further examined whether a correlation of the expression status of PCBP1 and CD44 v6 exists in primary HCCs. Real-time PCR analysis was performed to detect the mRNA levels of PCBP1 and CD44 v6 in HCC tissue and the adjacent non-cancerous liver tissues of 33 HCC patients. The result suggested that in HCC tissues, PCBP1 showed significant negative correlation with the expression of v6 (n = 33, r = -0.74689 p < 0.0001) (Figure 5A), that is, in HCC patients which PCBP1 was down-regulated compared to the non-cancerous liver tissue, the CD44 v6 expression level showed a significant up-regulation. However, no significant correlation was detected between PCBP1 expression and CD44 std expression in HCC (n = 24, r = 0.20696, p = 0.3319) (Figure 5B). These data suggested that the reduction of PCBP1 expression correlated with the up-regulation of CD44 v6 expression in HCC.


PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells.

Zhang T, Huang XH, Dong L, Hu D, Ge C, Zhan YQ, Xu WX, Yu M, Li W, Wang X, Tang L, Li CY, Yang XM - Mol. Cancer (2010)

Negative Correlation of PCBP1 and CD44 v6 mRNA expression in HCC tissue samples analyzed. Total RNA was extracted from HCC specimens and their adjacent non-cancerous liver tissues for real-time PCR analysis. The expression levels of PCBP1, v6 and std in non-cancerous tissues were set to 1 and normalized to GAPDH mRNA. The experiments in each sample were performed in triplicate with at least 3 independent times. The data was shown as the average of these experiments. Then Spearman test was performed.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2864215&req=5

Figure 5: Negative Correlation of PCBP1 and CD44 v6 mRNA expression in HCC tissue samples analyzed. Total RNA was extracted from HCC specimens and their adjacent non-cancerous liver tissues for real-time PCR analysis. The expression levels of PCBP1, v6 and std in non-cancerous tissues were set to 1 and normalized to GAPDH mRNA. The experiments in each sample were performed in triplicate with at least 3 independent times. The data was shown as the average of these experiments. Then Spearman test was performed.
Mentions: Since PCBP1 was a negative regulator of CD44 v6 expression and tumor invasion, we further examined whether a correlation of the expression status of PCBP1 and CD44 v6 exists in primary HCCs. Real-time PCR analysis was performed to detect the mRNA levels of PCBP1 and CD44 v6 in HCC tissue and the adjacent non-cancerous liver tissues of 33 HCC patients. The result suggested that in HCC tissues, PCBP1 showed significant negative correlation with the expression of v6 (n = 33, r = -0.74689 p < 0.0001) (Figure 5A), that is, in HCC patients which PCBP1 was down-regulated compared to the non-cancerous liver tissue, the CD44 v6 expression level showed a significant up-regulation. However, no significant correlation was detected between PCBP1 expression and CD44 std expression in HCC (n = 24, r = 0.20696, p = 0.3319) (Figure 5B). These data suggested that the reduction of PCBP1 expression correlated with the up-regulation of CD44 v6 expression in HCC.

Bottom Line: We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing.A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues.We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

View Article: PubMed Central - HTML - PubMed

Affiliation: Beijing Institute of Radiation Medicine, Beijing, 100850, China.

ABSTRACT

Background: PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive.

Results: We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing. Invasion assay suggested that PCBP1 played a negative role in tumor invasion and re-expression of v6 partly reversed the inhibition effect by PCBP1. A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues.

Conclusions: We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.

Show MeSH
Related in: MedlinePlus