MicroRNA-138 functions as a tumor suppressor in osteosarcoma by targeting differentiated embryonic chondrocyte gene 2.
BACKGROUND
MicroRNA-138 (miR-138) has been proven to be a tumor suppressor gene in various types of tumors. However, the expression and the role of miR-138 in human osteosarcoma are still poorly understood. We investigated the function and the underlying mechanism of miR-138 in osteosarcoma.


METHODS
The expression of miR-138 in human osteosarcoma tissues and cell lines was detected by real-time PCR analysis. The gain-of-function and loss-of-function experiments were performed on osteosarcoma cell lines to investigate the effects of miR-138 on osteosarcoma progression, and to determine whether differentiated embryonic chondrocyte gene 2 (DEC2) mediates these effects. Cell proliferation, apoptosis and invasion were assessed by MTT, flow cytometry and transwell-matrigel assays. Dual-luciferase reporter assay was used to identify whether DEC2 is a direct target of miR-138.


RESULTS
MiR-138 was significantly downregulated in human osteosarcoma tissues and cell lines. Moreover, miR-138 expression was significantly lower in metastatic osteosarcoma tissues than that in non-metastatic tissues. The in vitro gain-of-function and loss-of-function experiments demonstrated that miR-138 inhibited cell proliferation and invasion, and promoted cell apoptosis of human osteosarcoma cells. DEC2 was verified as a direct target of miR-138, and DEC2 could reverse the inhibitory effect of miR-138 on osteosarcoma progression.


CONCLUSIONS
These findings suggested that miR-138 acts as a tumor suppressor in osteosarcoma.miR-138 inhibited cell proliferation and invasion, as well as promoted cell apoptosis of human osteosarcoma cells, at least partially, by inhibiting the expression of DEC2. MiR-138/DEC2 may be a novel therapeutic target in osteosarcoma.
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China. baoen_jiang@163.com.
Baoen
B
Jiang
Department of Traumatic Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong University, No 324 Jingwuweiqi Road, Jinan, 250021, Shandong, China.
Weidong
W
Mu
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Jiangquan
J
Wang
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Jianshu
J
Lu
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Shanyong
S
Jiang
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Liang
L
Li
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Haining
H
Xu
Department of Traumatic Orthopaedics, The People 's Hospital of Dongying City of Shandong Province, No 317 Nanyi Road, Dongying, 257091, Shandong, China.
Hongyan
H
Tian
D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D001859:Bone Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D035683:MicroRNAs; C422085:BHLHE41 protein, human; C546110:MIRN138 microRNA, human
Apoptosis; Differentiated embryonic chondrocyte gene 2; Invasion; MicroRNA-138; Osteosarcoma; Proliferation