Long Noncoding RNA NORAD Promotes Fracture Healing through Interacting with Osteoblast Differentiation via Targeting miR-26a.

The present study was designed to evaluate the dynamic expression of lncRNA NORAD in fracture healing of patients with brittle fractures and explore the function and mechanism of NORAD in regulating osteoblastic proliferation, differentiation, and apoptosis. The expression level of NORAD was detected by quantitative real-time PCR. The proliferation, differentiation, and apoptosis of osteoblasts were analyzed by MTT assay, ELISA, and flow cytometry. Luciferase report analysis was used to confirm the interaction between NORAD and its target ceRNA miR-26a. This study showed no significant differences in serum NORAD expression on the 7th day during fracture healing in patients, but increased expression of NORAD was certified on the 14, 21, and 28 days after fixation. Overexpression of NORAD promoted the proliferation and differentiation of osteoblasts and suppressed the apoptosis of osteoblasts. miR-26a proved to be the target gene of NORAD and was inhibited by overexpression of NORAD in osteoblasts. The enhanced expression of miR-26a was negatively linked to the lessened expression of NORAD. NORAD could accelerate the proliferation and differentiation of osteoblasts and inhibit apoptosis, thereby promoting fracture healing.

MicroRNA-455-3p promotes osteoblast differentiation via targeting HDAC2.

BACKGROUND: Fragility fracture commonly occurs in the elderly, the basis of fracture healing is osteoblast regeneration. The study measured the expression changes of microRNA-455-3p during fracture healing in patients with fragility fractures, and explored its influence on osteoblast differentiation. METHODS: 108 postmenopausal women with osteoporosis were recruited, in which 58 cases with fragility fracture. qRT-PCR was used for the measurement of miR-455-3p levels. MC3T3-E1 cells were induced differentiation by BMP-2. ELISA was performed for the measurement of alkaline phosphates (ALP), runt-related transcription factor-2 (RUNX2), osteocalcin (OCN), and Collagen I. Luciferase reporter gene assay was done for the target gene analysis. RESULTS: Serum miR-455-3p was significantly decreased in both osteoporosis and fragility fracture patients compared with the control group, which was most deficient in patients with fragility fracture. With the extension of treatment time, the level of miR-455-3p in serum increased gradually and reached the highest level at 4 weeks of treatment. Levels of miR-455-3p continued to increase on the 7th and 14th days after induction of cell differentiation. MiR-455-3p overexpression promoted cell proliferation, and increased the levels of osteoblast differentiation markers, including ALP, OCN, Collagen I, and RUNX2. MiR-455-3p in MC3T3-E1 cells was directly bound to HDAC2 and negatively regulated. Both MC3T3-E1 differentiation and the fracture healing of patients were accompanied by progressively reduced HDAC2. CONCLUSIONS: MiR-455-3p promotes osteogenic differentiation which may be associated with fracture healing, HDAC2 acts as a target of miR-455-3p in the underlying mechanism.

miR-876-3p suppresses the progression of colon cancer and correlates the prognosis of patients.

BACKGROUND: miR-876-3p has been identified to be downregulated in colon cancer, implying the potential biological function in the progression and prognosis of colon cancer. The clinical significance and the biological function of miR-876-3p were investigated in this study to assess the potential of miR-876-3p in acting as a novel biomarker of the progression of colon cancer. METHODS: The expression of miR-876-3p in colon cancer was evaluated by RT-qPCR. The clinical significance of miR-876-3p was assessed by associated its expression level with the clinical features and prognosis of patients. The biological function of miR-876-3p was estimated by the CCK8 and Transwell assay in vitro. RESULTS: The significant downregulation of miR-876-3p was observed in colon cancer tissues and cells, which was closely associated with the lymph node metastasis status, TNM stage, and the perineural invasion of patients. miR-876-3p served as an independent indicator that was negatively associated with the prognosis of patients. In colon cancer cells, miR-876-3p showed significant inhibitory effects on cell proliferation, migration, and invasion, indicating its tumor suppressor role in the progression of colon cancer. CONCLUSION: miR-876-3p might be involved in colon cancer development, which provides a potential therapeutic target for colon cancer treatment.