Tumor-suppressive microRNAs (miR-26a/b, miR-29a/b/c and miR-218) concertedly suppressed metastasis-promoting LOXL2 in head and neck squamous cell carcinoma.
In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall survival rate for patients with head and neck squamous cell carcinoma (HNSCC) is very poor (only 15-45%). Understanding the molecular mechanisms of metastatic pathways underlying HNSCC using currently available genomic approaches might improve therapies for and prevention of the disease. Our previous studies showed that three tumor-suppressive microRNAs (miRNAs), miR-26a/b, miR-29a/b/c and miR-218, significantly inhibited cancer cell migration and invasion. Therefore, we hypothesized that these miRNAs-regulated target genes deeply contributed to cancer metastasis. These tumor-suppressive miRNAs directly regulate LOXL2 expression in HNSCC cells by using in silico analysis and luciferase reporter assays. Overexpressed LOXL2 was confirmed in HNSCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in HNSCC cell lines. Our present data showed that tumor-suppressive miRNAs regulation of LOXL2 will provide new insights into the novel molecular mechanisms of HNSCC metastasis.
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Ichiro
I
Fukumoto
Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Naoko
N
Kikkawa
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Ryosuke
R
Matsushita
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Mayuko
M
Kato
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Akira
A
Kurozumi
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Rika
R
Nishikawa
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Yusuke
Y
Goto
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.|Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Keiichi
K
Koshizuka
Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Toyoyuki
T
Hanazawa
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Hideki
H
Enokida
Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Masayuki
M
Nakagawa
Department of Otorhinolaryngology/Head and Neck Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
Yoshitaka
Y
Okamoto
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Naohiko
N
Seki
D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D000077195:Squamous Cell Carcinoma of Head and Neck
D000594:Amino Acid Oxidoreductases; D035683:MicroRNAs; C547471:MIRN218 microRNA, human; C528163:MIRN26 microRNA, human; C532045:MIRN29a microRNA, human; C119091:LOXL2 protein, human