title: Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma.
abstract: Lung cancer remains the most frequent cause of cancer-related death in developed countries. A recent molecular-targeted strategy has contributed to improvement of the remarkable effect of adenocarcinoma of the lung. However, such treatment has not been developed for squamous cell carcinoma (SCC) of the disease. Our recent studies of microRNA (miRNA) expression signatures of human cancers showed that the microRNA-29 family (miR‑29a, miR‑29b and miR‑29c) significantly reduced cancer tissues compared to normal tissues. These findings suggest that miR‑29s act as tumor-suppressors by targeting several oncogenic genes. The aim of the study was to investigate the functional significance of miR‑29s in lung SCC and to identify miR‑29s modulating molecular targets in lung SCC cells. Restoration of all mature members of the miR‑29s inhibited cancer cell migration and invasion. Gene expression data combined in silico analysis and luciferase reporter assays demonstrated that the lysyl oxidase-like 2 (LOXL2) gene was a direct regulator of tumor‑suppressive miR‑29s. Moreover, overexpressed LOXL2 was confirmed in lung SCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in lung SCC cell lines. Our present data suggested that loss of tumor-suppressive miR‑29s enhanced cancer cell invasion in lung SCC through direct regulation of oncogenic LOXL2. Elucidation of the novel lung SCC molecular pathways and targets regulated by tumor-suppressive miR‑29s will provide new insights into the potential mechanisms of oncogenesis and metastasis of the disease.
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Seki
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mataki
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Matsushita
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kamikawaji
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kumamoto
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takagi
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Goto
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nishikawa
authors.affiliation: Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Enokida
authors.affiliation: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8520, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics
chemical_list: C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human