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

Mariko Mine; Kojiro Yamaguchi; Tsuyoshi Sugiura; Satomi Chigita; Naoya Yoshihama; Rumi Yoshihama; Naomi Hiyake; Yosuke Kobayashi; Yoshihide Mori

doi:10.1371/journal.pone.0131350

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

PLoS One. 2015 Jul 1;10(7):e0131350. doi: 10.1371/journal.pone.0131350. eCollection 2015.

Authors

Mariko Mine¹, Kojiro Yamaguchi², Tsuyoshi Sugiura², Satomi Chigita¹, Naoya Yoshihama¹, Rumi Yoshihama¹, Naomi Hiyake¹, Yosuke Kobayashi¹, Yoshihide Mori¹

Affiliations

¹ 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.
² Department of Maxillofacial Diagnostic and Surgical Science, Field of Oral and Maxillofacial Rehabilitation, Graduate School of Dental Science, Kagoshima University Sakuragaoka, Kagoshima, 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Membrane / chemistry
Cell Membrane / metabolism
Cell Movement
Epithelial Cells / metabolism*
Epithelial Cells / pathology
Frizzled Receptors / genetics*
Frizzled Receptors / metabolism
Gene Expression Regulation, Neoplastic*
Humans
Kangai-1 Protein / genetics*
Kangai-1 Protein / metabolism
Lung / metabolism
Lung / pathology
MicroRNAs / genetics*
MicroRNAs / metabolism
Oligonucleotides, Antisense / genetics
Oligonucleotides, Antisense / metabolism
Plasmids / chemistry
Plasmids / metabolism
Transfection
Wnt Signaling Pathway
beta Catenin / genetics
beta Catenin / metabolism

Substances

CD82 protein, human
CTNNB1 protein, human
FZD2 protein, human
Frizzled Receptors
Kangai-1 Protein
MIRN203 microRNA, human
MIRN338 microRNA, human
MicroRNAs
Oligonucleotides, Antisense
beta Catenin

Grants and funding

This study was supported by Grants-in Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKEN, grant no. 23390465 and 15H05045 to TS; grant no. 25893174 to SC; and grant no. 25861958 to YK) (http://kaken.nii.ac.jp/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.