Limits...
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

miR-203 targeted the FZD2 gene.The FZD2 3′-UTR sequence and complementary miR-203-binding sequences are shown.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4488846&req=5

pone.0131350.g008: miR-203 targeted the FZD2 gene.The FZD2 3′-UTR sequence and complementary miR-203-binding sequences are shown.

Mentions: The mechanisms regulating FZD expression have not been elucidated. Recently, researchers have reported that FZD is regulated by miRNAs [16,17]. Therefore, in this study, we analyzed the effects of miRNAs on FZD expression. Using the miRanda algorithm [13,14], we predicted 11 candidate miRNAs that targeted specific FZDs. Of these, miR-203 and mir-338-3p were regulated by CD82 overexpression. After subsequent analyses, only miR-203 inhibited FZD2 expression at the mRNA and protein levels. As shown in Fig 8, FZD2 had one potential complimentary miR-203-binding site within its 3′-UTR, suggesting that FZD2 was targeted by miR-203. Additionally, target inhibition assays designed for this binding site revealed that miR-203 targeted FZD2 mRNA directly. Moreover, miR-203 also regulated cell migration, a critical component of metastatic progression, in cancer cells through CD82. Thus, our data provided important insights into the regulation of the Wnt signaling pathway by miRNAs in cancer 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)

miR-203 targeted the FZD2 gene.The FZD2 3′-UTR sequence and complementary miR-203-binding sequences are shown.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131350.g008: miR-203 targeted the FZD2 gene.The FZD2 3′-UTR sequence and complementary miR-203-binding sequences are shown.
Mentions: The mechanisms regulating FZD expression have not been elucidated. Recently, researchers have reported that FZD is regulated by miRNAs [16,17]. Therefore, in this study, we analyzed the effects of miRNAs on FZD expression. Using the miRanda algorithm [13,14], we predicted 11 candidate miRNAs that targeted specific FZDs. Of these, miR-203 and mir-338-3p were regulated by CD82 overexpression. After subsequent analyses, only miR-203 inhibited FZD2 expression at the mRNA and protein levels. As shown in Fig 8, FZD2 had one potential complimentary miR-203-binding site within its 3′-UTR, suggesting that FZD2 was targeted by miR-203. Additionally, target inhibition assays designed for this binding site revealed that miR-203 targeted FZD2 mRNA directly. Moreover, miR-203 also regulated cell migration, a critical component of metastatic progression, in cancer cells through CD82. Thus, our data provided important insights into the regulation of the Wnt signaling pathway by miRNAs in cancer 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