MicroRNA-214 inhibits the osteogenic differentiation of human osteoblasts through the direct regulation of baculoviral IAP repeat-containing 7
EXPERIMENTAL CELL RESEARCH
Authors: Liu, Jianmin; Li, Yan; Luo, Ming; Yuan, Zhi; Liu, Jian
Abstract
Osteoblasts and osteoclasts coordinate to monitor the dynamic osteogenic balance between bone formation and bone resorption. Hence, an investigation of the regulatory mechanisms underlying osteogenic osteoblast differentiation will provide more methods for bone repair and bone regeneration. In the present study, human osteoblast hFOB 1.19 cells were cultured. MicroRNA-214 (miR-214) expression significantly down-regulated during the osteogenic differentiation of hFOB 1.19 cells. In addition, miR-214 overexpression by miR-214 precursor transfection markedly inhibited the expression of alkaline phosphatase (ALP), collagen type I alpha 1 (col1 alpha 1) and runt-related transcription factor 2 (Runx2), which concomitantly decreased ALP activity and the number of mineralized nodules but promoted the expression of signal transducer and activator of transcription 1 (STAT1), an osteogenesis blocker. We next found that miR-214 inhibited the expression of baculoviral IAP repeat-containing 7 (BIRC7), a member of the inhibitor of apoptosis proteins family. However, BIRC7 overexpression, which was induced by plasmid transfection, notably reversed the inhibitory effects of miR-214, indicating a potential BIRC7-dependent osteogenic differentiation manner mediated by miR-214. Taken together, our results demonstrate for the first time that miR-214 suppresses osteogenesis by targeting BIRC7, providing a possible therapeutic target for bone degenerative diseases.
Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder
NEOPLASMA
Authors: Yuan, Y.; Yang, Z. L.; Zou, Q.; Li, J. H.; Li, D. Q.; Liang, L. F.; Zeng, G. X.; Chen, S. L.
Abstract
Gallbladder cancers (GBCs) are uncommon, but highly aggressive cancers. The majority of GBCs are adenocarcinomas (ACs), but rare subtypes of GBCs such as squamous cell carcinoma (SC) and adenosquamous carcinoma (ASC) are observed as well. The clinicopathological characteristics of SC/ASC have not been well documented. Expressions of BIRC7 and STC2 were observed in some tumors. However, BIRC7 and STC2 expressions and clinical significances in gallbladder cancer have not been reported. In this study, the protein expressions of BIRC7 and STC2 in 46 SCs/ASCs and 80 ACs were measured using immunohistochemistry. We demonstrated that positive BIRC7 and STC2 expressions were significantly associated with large tumor mass (>3cm), high TNM stage and lymph node metastasis in SC/ASC and AC (p<0.05). Positive expression of BIRC7 was significantly associated with invasion of around tissues and organs in both SC/ASC and AC. Additionally, negative BIRC7 and STC2 expressions were significantly associated with surgical curability in AC. Univariate Kaplan-Meier analysis showed that BIRC7 and STC2 expressions, differentiation, tumor size, TNM stages, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients(p < 0.001). Multivariate Cox regression analysis showed that positive BIRC7 and STC2 expressions are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive BIRC7 and STC2 expressions are closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer.