MiR-424/503-mediated Rictor upregulation promotes tumor progression

Chitose Oneyama; Yoriko Kito; Rei Asai; Jun-ichiro Ikeda; Takuya Yoshida; Daisuke Okuzaki; Rie Kokuda; Kyoko Kakumoto; Ken-ichi Takayama; Satoshi Inoue; Eiichi Morii; Masato Okada

doi:10.1371/journal.pone.0080300

MiR-424/503-mediated Rictor upregulation promotes tumor progression

PLoS One. 2013 Nov 11;8(11):e80300. doi: 10.1371/journal.pone.0080300. eCollection 2013.

Authors

Chitose Oneyama¹, Yoriko Kito, Rei Asai, Jun-ichiro Ikeda, Takuya Yoshida, Daisuke Okuzaki, Rie Kokuda, Kyoko Kakumoto, Ken-ichi Takayama, Satoshi Inoue, Eiichi Morii, Masato Okada

Affiliation

¹ Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Abstract

mTOR complex 2 (mTORC2) signaling is upregulated in multiple types of human cancer, but the molecular mechanisms underlying its activation and regulation remain elusive. Here, we show that microRNA-mediated upregulation of Rictor, an mTORC2-specific component, contributes to tumor progression. Rictor is upregulated via the repression of the miR-424/503 cluster in human prostate and colon cancer cell lines that harbor c-Src upregulation and in Src-transformed cells. The tumorigenicity and invasive activity of these cells were suppressed by re-expression of miR-424/503. Rictor upregulation promotes formation of mTORC2 and induces activation of mTORC2, resulting in promotion of tumor growth and invasion. Furthermore, downregulation of miR-424/503 is associated with Rictor upregulation in colon cancer tissues. These findings suggest that the miR-424/503-Rictor pathway plays a crucial role in tumor progression.

Publication types

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

MeSH terms

Carrier Proteins / genetics
Carrier Proteins / metabolism*
Cell Line, Tumor
Colonic Neoplasms / genetics
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology
Cytoskeleton / metabolism
Female
Gene Expression Regulation, Neoplastic / genetics
Gene Expression Regulation, Neoplastic / physiology
Humans
Male
Mechanistic Target of Rapamycin Complex 2
MicroRNAs / genetics
MicroRNAs / metabolism*
Multiprotein Complexes / genetics
Multiprotein Complexes / metabolism
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism
Prostatic Neoplasms / pathology
Rapamycin-Insensitive Companion of mTOR Protein
TOR Serine-Threonine Kinases / genetics
TOR Serine-Threonine Kinases / metabolism

Substances

Carrier Proteins
MIRN424 microrna, human
MIRN503 microRNA, human
MicroRNAs
Multiprotein Complexes
RICTOR protein, human
Rapamycin-Insensitive Companion of mTOR Protein
Mechanistic Target of Rapamycin Complex 2
TOR Serine-Threonine Kinases

Grants and funding

This work was supported by a Grant-in-aid for P-DIRECT from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by The Exciting Leading-Edge Research Project at Osaka University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.