MiR-125b inhibits stromal cell proliferation in giant cell tumor of bone by targeting parathyroid hormone 1 receptor.
OBJECTIVE
miR-125b has been identified as a tumor suppressor in many tumors, but its role in giant cell tumor (GCT) of bone remains poorly understood. The current study aimed to investigate the potential role and mechanism of miR-125b in GCT.


METHODS
Expression levels of miR-125b in GCT tissues were determined using RT-PCR. The cell proliferation was surveyed by direct cell counting, MTS and CCK-8, and the apoptotic cells were evaluated by Annexin V-FITC and propidium iodine staining assay. The target gene expression was determined using RT-PCR and western blot. Parathyroid hormone 1 receptor (PTH1R) 3'-UTR was cloned into luciferase reporter plasmid to confirm direct targeting.


RESULTS
We found that miR-125b was significantly down-regulated in GCT tissues. Using both gain- and loss-of-function analyses, we further revealed that miR-125b suppressed GCT stromal cell proliferation and induced cell apoptosis. Furthermore, we revealed that PTH/PTHrP type 1 receptor is a direct and functional target of miR-125b.


CONCLUSIONS
Our results suggest that miR-125b acts as a tumor suppressor through suppression of the PTH1R/RANKL signaling pathway. These findings contribute to our understanding of the functions of miR-125b in GCT.
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Pan-Feng
PF
Wu
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Jie-Yu
JY
Liang
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Fang
F
Yu
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Zheng-Bing
ZB
Zhou
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Ju-Yu
JY
Tang
Department of Orthopaedics, Xiang Ya Hospital, Central South University, Changsha 410008, China.
Kang-Hua
KH
Li
Cell proliferation; GCT; PTH1R; RANKL; miR-125b