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miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells.

Mine M, Yamaguchi K, Sugiura T, Chigita S, Yoshihama N, Yoshihama R, Hiyake N, Kobayashi Y, Mori Y - PLoS ONE (2015)

Bottom Line: In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs).Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells.Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Division of Maxillofacial Diagnostic and Surgical Sciences, Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University Maidashi, Higashi-ku, Fukuoka, Japan.

ABSTRACT
CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.

No MeSH data available.


Related in: MedlinePlus

Effects of miR-203 and miR-338-3p transfection on the migration of h1299 cells.(A–F) Cell migration was evaluated using wound healing assays, as described in the Materials and Methods. Randomly chosen wound fields were photographed every 8 h for 24 h. (G, H) Wound areas were evaluated using the following formula: wound area (%) = wound area after the indicated period × 100 / initial wound area. (I) Migration ability was evaluated based on the wound area. The experiments were performed in triplicate, and the data were calculated as means ± SDs. The statistical significance of differences was analyzed using the Student’s t-test. *P < 0.01, **P < 0.05.
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pone.0131350.g007: Effects of miR-203 and miR-338-3p transfection on the migration of h1299 cells.(A–F) Cell migration was evaluated using wound healing assays, as described in the Materials and Methods. Randomly chosen wound fields were photographed every 8 h for 24 h. (G, H) Wound areas were evaluated using the following formula: wound area (%) = wound area after the indicated period × 100 / initial wound area. (I) Migration ability was evaluated based on the wound area. The experiments were performed in triplicate, and the data were calculated as means ± SDs. The statistical significance of differences was analyzed using the Student’s t-test. *P < 0.01, **P < 0.05.

Mentions: To elucidate the functional effects of FZD2 downregulation by miR-203, cell migration was quantitatively examined by wound healing assay. The miR-203 mimic inhibited cell migration in h1299/zeo cells (Fig 7A, 7B and 7G), while the miR-203 inhibitor induced cell migration in h1299/CD82 cells (Fig 7D, 7E and 7H). In contrast, miR-338-3p did not affect h1299 cell migration (Fig 7A, 7C, 7D and 7F). Fig 7I shows the inhibition of migration in h1299 cells. Overexpression of CD82 reduced cell migration to approximately 60% that of h1299/zeo cells. The miR-203 mimic inhibited migration in h1299/zeo cells, and the miR-203 inhibitor induced migration in h1299/CD82 cells, reaching approximately 80% that of h1299/zeo cells.


miR-203 Inhibits Frizzled-2 Expression via CD82/KAI1 Expression in Human Lung Carcinoma Cells.

Mine M, Yamaguchi K, Sugiura T, Chigita S, Yoshihama N, Yoshihama R, Hiyake N, Kobayashi Y, Mori Y - PLoS ONE (2015)

Effects of miR-203 and miR-338-3p transfection on the migration of h1299 cells.(A–F) Cell migration was evaluated using wound healing assays, as described in the Materials and Methods. Randomly chosen wound fields were photographed every 8 h for 24 h. (G, H) Wound areas were evaluated using the following formula: wound area (%) = wound area after the indicated period × 100 / initial wound area. (I) Migration ability was evaluated based on the wound area. The experiments were performed in triplicate, and the data were calculated as means ± SDs. The statistical significance of differences was analyzed using the Student’s t-test. *P < 0.01, **P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4488846&req=5

pone.0131350.g007: Effects of miR-203 and miR-338-3p transfection on the migration of h1299 cells.(A–F) Cell migration was evaluated using wound healing assays, as described in the Materials and Methods. Randomly chosen wound fields were photographed every 8 h for 24 h. (G, H) Wound areas were evaluated using the following formula: wound area (%) = wound area after the indicated period × 100 / initial wound area. (I) Migration ability was evaluated based on the wound area. The experiments were performed in triplicate, and the data were calculated as means ± SDs. The statistical significance of differences was analyzed using the Student’s t-test. *P < 0.01, **P < 0.05.
Mentions: To elucidate the functional effects of FZD2 downregulation by miR-203, cell migration was quantitatively examined by wound healing assay. The miR-203 mimic inhibited cell migration in h1299/zeo cells (Fig 7A, 7B and 7G), while the miR-203 inhibitor induced cell migration in h1299/CD82 cells (Fig 7D, 7E and 7H). In contrast, miR-338-3p did not affect h1299 cell migration (Fig 7A, 7C, 7D and 7F). Fig 7I shows the inhibition of migration in h1299 cells. Overexpression of CD82 reduced cell migration to approximately 60% that of h1299/zeo cells. The miR-203 mimic inhibited migration in h1299/zeo cells, and the miR-203 inhibitor induced migration in h1299/CD82 cells, reaching approximately 80% that of h1299/zeo cells.

Bottom Line: In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs).Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells.Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.

View Article: PubMed Central - PubMed

Affiliation: Division of Maxillofacial Diagnostic and Surgical Sciences, Department of Oral and Maxillofacial Surgery, Graduate School of Dental Science, Kyushu University Maidashi, Higashi-ku, Fukuoka, Japan.

ABSTRACT
CD82/KAI1, a member of the tetraspanin superfamily, is a suppressor of metastasis and CD82 inhibits canonical Wnt signaling via downregulation of several Frizzled (FZD) isoforms, resulting in accumulation of β-catenin at the cell membrane. In this study, we investigated the mechanism through which CD82 inhibited FZD expression by examining the effects of microRNAs (miRNAs). The miRanda algorithm predicted 11 miRNAs from FZD sequences. Among these miRNAs, CD82 caused upregulation of miR-203 (by 2.095-fold) and downregulation of miR-338-3p (by 0.354-fold) as compared with control cells. Transfection with miR-203 and miR338-3p mimics or inhibitors revealed that miR-203 downregulated FZD2 mRNA (by 0.268-fold) and protein expression (by 0.701-fold). Moreover, transfection with the miR-203 mimic also inhibited cell migration. Therefore, these findings suggested that CD82 enhanced the expression of miR-203 and directly downregulate FZD2 expression, suppressing cancer metastasis by inhibition of the Wnt signaling pathway.

No MeSH data available.


Related in: MedlinePlus