Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma

Rika Nishikawa; Takeshi Chiyomaru; Hideki Enokida; Satoru Inoguchi; Tomoaki Ishihara; Ryosuke Matsushita; Yusuke Goto; Ichiro Fukumoto; Masayuki Nakagawa; Naohiko Seki

doi:10.1016/j.febslet.2015.06.005

Tumour-suppressive microRNA-29s directly regulate LOXL2 expression and inhibit cancer cell migration and invasion in renal cell carcinoma

FEBS Lett. 2015 Jul 22;589(16):2136-45. doi: 10.1016/j.febslet.2015.06.005. Epub 2015 Jun 19.

Affiliations

¹ Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
² Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
³ Department of Functional Genomics, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. Electronic address: naoseki@faculty.chiba-u.jp.

PMID: 26096783
DOI: 10.1016/j.febslet.2015.06.005

Abstract

Here, we found that members of the microRNA-29 family (miR-29a/b/c; "miR-29s") were significantly reduced in clear cell renal cell carcinoma (ccRCC) tissues, suggesting that they functioned as tumour suppressors. Restoration of all mature members of the miR-29 family inhibited cancer cell proliferation, migration and invasion. LOXL2 was a direct target gene of miR-29s, as shown by genome-wide gene expression analysis and luciferase reporter assay. Overexpressed LOXL2 was confirmed in ccRCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in ccRCC cell lines. Our data demonstrated that the miR-29s-LOXL2 axis contributed to cancer cell migration and invasion in ccRCC.

Keywords: Clear cell renal cell carcinoma; LOXL2; miR-29a; miR-29b; miR-29c; microRNA.

Publication types

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

MeSH terms

Amino Acid Oxidoreductases / antagonists & inhibitors*
Amino Acid Oxidoreductases / genetics
Amino Acid Oxidoreductases / metabolism
Carcinoma, Renal Cell / metabolism*
Carcinoma, Renal Cell / pathology
Carcinoma, Renal Cell / surgery
Cell Line, Tumor
Cell Movement
Cell Proliferation
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Silencing*
Genes, Reporter
Genome-Wide Association Study
Humans
Kidney / metabolism
Kidney / pathology
Kidney / surgery
Kidney Neoplasms / metabolism*
Kidney Neoplasms / pathology
Kidney Neoplasms / surgery
Male
MicroRNAs / metabolism*
Neoplasm Grading
Neoplasm Invasiveness
Neoplasm Proteins / antagonists & inhibitors*
Neoplasm Proteins / genetics
Neoplasm Proteins / metabolism
Neoplasm Staging
Nephrectomy
RNA, Neoplasm / metabolism*
RNA, Small Interfering
Recombinant Proteins / chemistry
Recombinant Proteins / metabolism

Substances

MIRN29a microRNA, human
MicroRNAs
Neoplasm Proteins
RNA, Neoplasm
RNA, Small Interfering
Recombinant Proteins
Amino Acid Oxidoreductases
LOXL2 protein, human