Dysregulated long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) play key roles in the development of human cancers. The lncRNA growth arrest-specific 5 (GAS5) is reported to be a tumor suppressor in multiple cancers. However, the roles of GAS5 and its related miRNAs in osteosarcoma are poorly understood. This study explored the potential functions and mechanisms of GAS5 in the tumorigenesis of osteosarcoma. Here, the expression of GAS5, miR-221 and aplasia Ras homologue member I (ARHI) was determined in osteosarcoma tissues and cells by Real-time PCR (RT-qPCR). The underlying mechanism of GAS5 in osteosarcoma growth was analyzed via MTT, Transwell, RT-qPCR, Western blot, dual-luciferase reporter assay, RNA immunoprecipitation, and xenograft models after GAS5 overexpression. GAS5 and ARHI levels were significantly reduced, while miR-221 increased, both in osteosarcoma tissues and cells. Overexpression of GAS5 suppressed the proliferation, migration, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells. GAS5 could directly bind to miR-221 to decrease miR-221 expression and enhance ARHI expression. The effect of GAS5 overexpression on the proliferation, migration and EMT was reversed by miR-221 mimics or ARHI siRNA in osteosarcoma cells. Additionally, GAS5 suppressed tumor volume, Ki-67 and PCNA staining, and EMT process in the development of osteosarcoma in vivo. Taken together, lncRNA GAS5 functions as a competing endogenous RNA for miR-221 to suppress cell growth and EMT in osteosarcoma by regulating the miR-221/ARHI pathway. J. Cell. Biochem. 118: 4772-4781, 2017. © 2017 Wiley Periodicals, Inc.

Prostate cancer has become the most commonly diagnosed and the second leading cause of cancer-related deaths in males. The long noncoding RNA second chromosome locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in a subset of prostate cancer. However, the significance and mechanism of SChLAP1 in prostate cancer are not well known. In this study, we explored the role of SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1 expression was significantly increased in prostate cancer cells and tissues. Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. In addition, a potential bonding site between miR-198 and SChLAP1 was predicted, and a low expression of miR-198 was found in prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased the expression of miR-198, and SChLAP1 overexpression markedly decreased it, indicating that SChLAP1 acted as a negative regulator in the expression of miR-198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and subsequently modulated the MAPK1 signaling pathway in prostate cancer. In conclusion, our study has identified a novel pathway through which SChLAP1 exerts its oncogenic role in prostate cancer at the level of miRNAs and provided a molecular basis for potential applications of SChLAP1 in the prognosis and treatment of prostate cancer.

Bone defects resulting from non-union fractures or tumour resections are common clinical problems. Long non-coding RNAs (lncRNAs) are reported to play vital roles in stem cell differentiation. The aim of this study was to elucidate the role of lncRNA-H19 in osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Following the establishment of an osteogenic differentiation model in rats, the expression of H19, microRNA-149 (miR-149) and stromal cell-derived factor-1 (SDF-1) was measured by RT-qPCR. Thereafter, BMMSCs were isolated from rats and treated with a series of mimic, inhibitor or siRNA. SDF-1 expression, alkaline phosphatase (ALP) activity and osteocalcin (OCN) content were detected. The mineralized and calcified nodules were assessed by alizarin red S and Von Kossa staining.BMMSC surface markers were detected by flow cytometry. Western blot analysis was used to measure the expression of ALP, OCN, runt-related transcription factor 2 (RUNX2) and osterix (OSX) proteins. Lastly, dual-luciferase reporter gene assay and RNA immunoprecipitation were applied to verify the relationship of H19, miR-149 and SDF-1. Overexpressed H19 and SDF-1 and poorly expressed miR-149 were found in rats with osteogenic differentiation. H19 increased SDF-1 expression by binding to miR-149. H19 enhanced ALP activity, OCN content, calcium deposit and ALP, OCN, RUNX2 and OSX protein expression of BMMSCS by up-regulating SDF-1 via binding to miR-149. Taken together, up-regulated H19 could promote the osteogenic differentiation of BMMSCs by increasing SDF-1 via miR-149.

This meta-analysis was conducted to study whether kinematically aligned total knee arthroplasty (TKA) improves short-term functional outcomes compared with mechanical alignment without changing the hip-knee-ankle angle. Prospective cohort studies were searched from electronic literature databases, including PubMed, Web of Science, Embase (Ovid interface), and Cochrane Library (Ovid interface). Total 1,159 records were identified. Six trials involving 561 patients were eligible for data extraction and meta-analysis. The included studies recorded outcomes in the follow-up range from 6 to 34 months. Primary outcomes were to assess the functional outcomes in follow-up, and KA group achieved better performance on WOMAC score (mean difference [MD] = -18.82, 95% CI: -16.06 to -5.58), knee function score (MD = 7.23, 95% CI: 0.52-13.94), Oxford knee score (MD = 4.76, 95% CI: 0.40-9.12), and knee range of flexion (MD = 4.48, 95% CI: 2.09-6.86), whereas other parameters including Knee Society score, knee range of extension, VAS pain score, and the occurrence of the complications were without significant difference ( > 0.05). Second outcomes evaluated the perioperative clinic indexes. Our meta-analysis showed that KA group had a shorter time of operation (MD = -15.44, 95% CI: -27.47 to -3.71) and a longer walk distance before discharge (MD = 53.24, 95% CI: 21.32-85.15) when compared with the MA group, whereas the change in hemoglobin, incision length, knee range of flexion before discharge, and length of stays were without significant difference ( > 0.05). Third outcomes were used to analyze the alignment data. Our study showed that KA had larger angles of femoral component and mechanical axis of the femur (MD = -1.95,95% CI: -2.77 to -1.13), tibial component and mechanical axis of tibia (MD = 2.06, 95% CI: 1.43-2.70), anatomic knee angle (MD = -0.72, 95% CI: -1.33 to -0.11), and operative limb alignment (MD = -1.97, 95% CI: -2.50 to -1.45,) compared with the MA group, but the hip-knee-ankle angles between the two groups were similar. KA provided better functional outcomes and better flexion following short-term follow-up of TKA. However, longer-term follow-up and larger sample studies are needed to put into research in the future.

The purpose of this study was to compare the efficacy of tissue-engineered periosteum (TEP) to allgeneic bone in repairing segmental bone defect. TEP was fabricated with osteoinduced rabbit bone marrow mesenchymal stem cells (MSCs) and porcine small intestinal submucosa (SIS). Allogrfats were cryopreserved radial segments of New Zealand Rabbits. Forty-eight radial critical-sized defects (CSD) were bilaterally produced in 24 rabbits. The defects were divided into three groups, group A, TEP implantation, group B, SIS implantation, and group C allograft. Bone defect reconstruction was kinetically analyzed at 4, 8, and 12 weeks by radiographic and histological scoring system. In group A, bone defects were radiographically and histologically healed with mature cortex and marrow cavity by 12 weeks, while none of the defects healed in group B. Group C showed a slow process of creeping substitution with lymphocyte infiltration. Statistical comparison confirmed that group A had a more efficient and rapid bone defect reparation as well as remodelling than Group B and C. In conclusion, TEP is superior to structural allograft in reconstruction of allogenic segmental bone defect. Pure SIS cannot guide bone regeneration in this rabbit model.