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miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC).

Kikkawa N, Hanazawa T, Fujimura L, Nohata N, Suzuki H, Chazono H, Sakurai D, Horiguchi S, Okamoto Y, Seki N - Br. J. Cancer (2010)

Bottom Line: Expression analysis identified 11 upregulated and 31 downregulated miRNAs.The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene.Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT

Background: Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive malignancy with one of the worst prognoses among all head and neck cancers. Greater understanding of the pertinent molecular oncogenic pathways could help improve diagnosis, therapy, and prevention of this disease. The aim of this study was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression signatures from clinical HSCC specimens, and to predict their biological target genes.

Methods: Expression levels of 365 human mature miRNAs from 10 HSCC clinical samples were screened using stem-loop real-time quantitative PCR. Downregulated miRNAs were used in cell proliferation assays to identify a tumour-suppressive miRNA. Genome-wide gene expression analyses were then performed to identify the target genes of the tumour-suppressive miRNA.

Results: Expression analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth in all head and neck cancer cell lines examined. The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the inhibition of cell proliferation in head and neck SCC cells.

Conclusion: Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.

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Related in: MedlinePlus

PTPN11 overexpression in clinical HSCC specimens. (A) PTPN11 mRNA expression levels were analysed by TaqMan quantitative real-time PCR and normalised to 18S rRNA expression. PTPN11 mRNA expression was compared between matched HSCC and non-cancerous tissues in 16 patients. Data were analysed using the paired t-test. N, non-cancerous tissues; C, cancer tissues. (B) Correlation between PTPN11 and miR-489 expression in HSCC clinical specimens.
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fig5: PTPN11 overexpression in clinical HSCC specimens. (A) PTPN11 mRNA expression levels were analysed by TaqMan quantitative real-time PCR and normalised to 18S rRNA expression. PTPN11 mRNA expression was compared between matched HSCC and non-cancerous tissues in 16 patients. Data were analysed using the paired t-test. N, non-cancerous tissues; C, cancer tissues. (B) Correlation between PTPN11 and miR-489 expression in HSCC clinical specimens.

Mentions: The mRNA expression levels of PTPN11 were significantly higher in 16 HSCC tissues than in adjacent non-cancerous hypopharyngeal tissues (Figure 5A). The possibility that the expression of PTPN11 and the miR-489 were correlated was tested using the Spearman rank correlation. However, the inverse correlation between PTPN11 and miR-489 expression levels was too low to be statistically significant (rs=−0.283 and P=0.11; Figure 5B).


miR-489 is a tumour-suppressive miRNA target PTPN11 in hypopharyngeal squamous cell carcinoma (HSCC).

Kikkawa N, Hanazawa T, Fujimura L, Nohata N, Suzuki H, Chazono H, Sakurai D, Horiguchi S, Okamoto Y, Seki N - Br. J. Cancer (2010)

PTPN11 overexpression in clinical HSCC specimens. (A) PTPN11 mRNA expression levels were analysed by TaqMan quantitative real-time PCR and normalised to 18S rRNA expression. PTPN11 mRNA expression was compared between matched HSCC and non-cancerous tissues in 16 patients. Data were analysed using the paired t-test. N, non-cancerous tissues; C, cancer tissues. (B) Correlation between PTPN11 and miR-489 expression in HSCC clinical specimens.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2966617&req=5

fig5: PTPN11 overexpression in clinical HSCC specimens. (A) PTPN11 mRNA expression levels were analysed by TaqMan quantitative real-time PCR and normalised to 18S rRNA expression. PTPN11 mRNA expression was compared between matched HSCC and non-cancerous tissues in 16 patients. Data were analysed using the paired t-test. N, non-cancerous tissues; C, cancer tissues. (B) Correlation between PTPN11 and miR-489 expression in HSCC clinical specimens.
Mentions: The mRNA expression levels of PTPN11 were significantly higher in 16 HSCC tissues than in adjacent non-cancerous hypopharyngeal tissues (Figure 5A). The possibility that the expression of PTPN11 and the miR-489 were correlated was tested using the Spearman rank correlation. However, the inverse correlation between PTPN11 and miR-489 expression levels was too low to be statistically significant (rs=−0.283 and P=0.11; Figure 5B).

Bottom Line: Expression analysis identified 11 upregulated and 31 downregulated miRNAs.The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene.Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.

View Article: PubMed Central - PubMed

Affiliation: Department of Functional Genomics, Graduate School of Medicine, Chiba University, Chiba, Japan.

ABSTRACT

Background: Hypopharyngeal squamous cell carcinoma (HSCC) is an aggressive malignancy with one of the worst prognoses among all head and neck cancers. Greater understanding of the pertinent molecular oncogenic pathways could help improve diagnosis, therapy, and prevention of this disease. The aim of this study was to identify tumour-suppressive microRNAs (miRNAs), based on miRNA expression signatures from clinical HSCC specimens, and to predict their biological target genes.

Methods: Expression levels of 365 human mature miRNAs from 10 HSCC clinical samples were screened using stem-loop real-time quantitative PCR. Downregulated miRNAs were used in cell proliferation assays to identify a tumour-suppressive miRNA. Genome-wide gene expression analyses were then performed to identify the target genes of the tumour-suppressive miRNA.

Results: Expression analysis identified 11 upregulated and 31 downregulated miRNAs. Gain-of-function analysis of the downregulated miRNAs revealed that miR-489 inhibited cell growth in all head and neck cancer cell lines examined. The gene PTPN11 coding for a cytoplasmic protein tyrosine phosphatase containing two Src Homology 2 domains was identified as a miR-489-targeted gene. Knockdown of PTPN11 resulted in the inhibition of cell proliferation in head and neck SCC cells.

Conclusion: Identification of the tumour-suppressive miRNA miR-489 and its target, PTPN11, might provide new insights into the underlying molecular mechanisms of HSCC.

Show MeSH
Related in: MedlinePlus