Occurrence Of Osteosarcoma Research Articles

LncRNA HOXA-AS3 promotes cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma

Osteosarcoma is an aggressive form of bone cancer and affects the health in children and adolescents. Although conventional treatment improves the osteosarcoma survival, some patients have metastasis and drug resistance, leading to a worse prognosis. Therefore, it is necessary to explore the molecular mechanism of osteosarcoma occurrence and progression, which could discover the novel treatment for osteosarcoma. Long noncoding RNAs (lncRNAs) have been reported to regulate osteosarcoma occurrence and malignant progression. LncRNA HOXA-AS3 facilitates the tumorigenesis and progression in a variety of human cancers. However, the underlying mechanism of lncRNA HOXA-AS3-induced oncogenesis is poorly determined in osteosarcoma. To address this point, we utilized several cellular biological strategies and molecular approaches to explore the biological functions and mechanisms of lncRNA HOXA-AS3 in osteosarcoma cells. We found that lncRNA HOXA-AS3 facilitates cell proliferation and invasion via targeting miR-218-5p/FOXP1 axis in osteosarcoma. In conclusion, lncRNA HOXA-AS3 could be a promising target for osteosarcoma treatment.

Approach to Diagnosis and Management of Osteosarcoma

Osteosarcoma is a primary bone malignancy of mesenchymal origin. The prevalence of osteosarcoma in Indonesia is not known with certainty. Studies have shown that Paget disease, electrical burns, trauma, beryllium exposure, exposure to alkylating agents, FBJ virus, osteo-chondromatosis, enchondromatosis, fibrous dysplasia, orthopedic prostheses, and bone fractures have been associated with the occurrence of osteosarcoma. Survival rates are expected to improve with treatment consisting of a combination or one of recently developed surgical resection,chemotherapy, and targeted immunotherapy.

Genome-wide identification of alternative splicing and splicing regulated in immune infiltration in osteosarcoma patients.

Background: Osteosarcoma typically occurs in adolescents, and the survival rate of patients with metastatic and recurrent osteosarcoma remains low. Abnormal regulation of alternative splicing is associated with the development of osteosarcoma. However, there is no genome-wide analysis of the function and regulatory mechanisms of aberrant alternative splicing associated with osteosarcoma. Methods: Published transcriptome data on osteosarcoma (GSE126209) derived from osteosarcoma patient tissue were downloaded. Gene expression profiling by high-throughput sequencing was performed on 9 normal samples and 10 tumor samples for genome-wide identification of osteosarcoma-related alternative splicing events. The potential function of osteosarcoma-associated alternative splicing events was examined by immune infiltration and correlation analysis. Regulation of aberrantly expressed RNA-binding proteins (RBPs) related to alternative splicing in osteosarcoma was clarified by co-expression analysis. Results: A total of 63 alternative splicing events, which are highly credible and dominant, were identified. GO enrichment analysis indicated that alternative splicing may be closely related to the immune response process. Immune infiltration analysis showed significant changes in the percentages of CD8 T cells, resting memory CD4 T cells, activated memory CD4 T cells, monocytes, resting dendritic cells, and activated mast cells in tumors compared to normal tissues, indicating the involvement of these immune cell types in the occurrence of osteosarcoma. Moreover, the analysis identified alternative splicing events that were co-altered with resting memory CD4 T cells, resting dendritic cells, and activated mast cells, events that may be associated with regulation of the osteosarcoma immune microenvironment. In addition, a co-regulatory network (RBP-RAS-immune) of osteosarcoma-associated RBPs with aberrant alternative splicing and altered immune cells was established. These RBPs include NOP58, FAM120C, DYNC1H1, TRAP1, and LMNA, which may serve as molecular targets for osteosarcoma immune regulation. Conclusion: These findings allow us to further understand the causes of osteosarcoma development and provide a new research direction for osteosarcoma immunotherapy or targeted therapy.

High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification.

Guanine nucleotide binding (G) protein subunit γ 4 (GNG4) is closely related to the malignant progression and poor prognosis of various tumours. However, its role and mechanism in osteosarcoma remain unclear. This study aimed to elucidate the biological role and prognostic value of GNG4 in osteosarcoma. Osteosarcoma samples in the GSE12865, GSE14359, GSE162454 and TARGET datasets were selected as the test cohorts. The expression level of GNG4 between normal and osteosarcoma was identified in GSE12865 and GSE14359. Based on the osteosarcoma single-cell RNA sequencing (scRNA-seq) dataset GSE162454, differential expression of GNG4 among cell subsets was identified at the single-cell level. As the external validation cohort, 58 osteosarcoma specimens from the First Affiliated Hospital of Guangxi Medical University were collected. Patients with osteosarcoma were divided into high- and low-GNG4 groups. The biological function of GNG4 was annotated using Gene Ontology, gene set enrichment analysis, gene expression correlation analysis and immune infiltration analysis. Kaplan-Meier survival analysis was conducted and receiver operating characteristic (ROC) curves were calculated to determine the reliability of GNG4 in predicting prognostic significance and diagnostic value. Functional in vitro experiments were performed to explore the function of GNG4 in osteosarcoma cells. GNG4 was generally highly expressed in osteosarcoma. As an independent risk factor, high GNG4 was negatively correlated with both overall survival and event-free survival. Furthermore, GNG4 was a good diagnostic marker for osteosarcoma, with an area under the receiver operating characteristic curve (AUC) of more than 0.9. Functional analysis suggested that GNG4 may promote the occurrence of osteosarcoma by regulating ossification, B-cell activation, the cell cycle and the proportion of memory B cells. In in vitro experiments, silencing of GNG4 inhibited the viability, proliferation and invasion of osteosarcoma cells. Through bioinformatics analysis and experimental verification, high expression of GNG4 in osteosarcoma was identified as an oncogene and reliable biomarker for poor prognosis. This study helps to elucidate the significant potential of GNG4 in carcinogenesis and molecular targeted therapy for osteosarcoma.

Sandwich biosensing on a nanodiamond-modified interdigitated electrode for monitoring the occurrence of osteosarcoma

BackgroundOsteosarcoma is a highly heterogeneous manifestation with varied subtypes and is diagnosed by imaging techniques; however, quantification of blood-based biomarkers boosts genuine osteosarcoma identification. MethodsHerein, a sensitive sandwich pattern with aptamer and antibody was conducted on a nanodiamond-modified interdigitated electrode surface to identify osteopintin, a well-suited biomarker for osteosarcoma. Diamond nanoparticles measured as 5±3 nm by a high-resolution microcopy were attached to the sensing surface through chemical [(3-aminopropyl)triethoxysilane, 1,1′-carbonyldiimidazole] and biological (biotin-streptavidin) linkers to immobilize the aptamer on the nanodiamond. The detection limit of osteopontin was attained to be 100 pM in phosphate-buffered saline (PBS)-spiked samples using a sandwich, and it was 1 nM with only aptamer at the coefficient determinations R2 values of 0.99 (y=1.2106x-1.0127) and 0.98 (y=1.0086x-0.7867), respectively, on linear concentrations of 0.1-100 nM osteopontin. Furthermore, biofouling experiments with complementary aptamer sequences, albumin and control samples did not increase the current responses, confirming the specific identification of osteopontin, which was further evidenced in serum-containing samples. Significant FindingsThis biosensing assay quantifies osteopontin at lower levels and diagnoses osteosarcoma.

Osteosarcoma Occurrence in Preclinical and Clinical Experiments with Teriparatide: A Qualitative Review

Osteosarcoma Occurrence in Preclinical and Clinical Experiments with Teriparatide: A Qualitative Review

Osteosarcoma with Orbital Metastasis in a Nigerian Child: A Case Report and Review of the Literature

Osteosarcoma is the most common primary bone tumour with a peak occurrence in adolescence. The occurrence of osteosarcoma in preadolescents is rare with a paucity of data in the developing world. Metastasis of osteosarcoma to the orbit is even a rarer presentation with few cases reported in the literature but to the best of the researchers’ knowledge, none of the previous cases had contralateral orbital metastasis to osteosarcoma. This is the first case report of orbital metastasis of osteosarcoma in Nigeria. The present case is presented for its rarity, to increase awareness and add to knowledge on the possibility of metastasis to contralateral orbit in osteosarcoma.

Osteosarcoma Cell-Derived Exosomal miR-1307 Promotes Tumorgenesis via Targeting AGAP1.

The occurrence of osteosarcoma (OS) is associated with abnormal expression of many microRNAs (miRNAs). Exosomal miRNAs get much more attentions in intracellular communications. miR-1307 has been studied in many cancers, but its effects in OS have not been studied. We hypothesized that OS-derived exosomal miR-1307 regulates OS tumorigenesis. First, we found OS cell-derived exosomes (Exos) significantly promoted the proliferation, migration, and invasion of OS cells. Secondly, we found miR-1307 was highly expressed in OS cell-derived exosomes (OS-Exos), human OS tissues, and OS cell lines. Then, OS-Exos were extracted after OS cells were cultured and transfected with miR-1307 inhibitor, and the level of miR-1307 in OS-Exos was significantly reduced. When the level of miR-1307 in OS-Exos was significantly reduced, the effects of OS-Exos on migration, invasion, and proliferation of OS cells were also significantly weakened. Furthermore, using TargetScan, miRDB, and mirDIP databases, we identified that AGAP1 was a target gene of miR-1307. Overexpression of miR-1307 could inhibit the expression of AGAP1 gene. We also found AGAP1 was lower expressed in human OS tissues and OS cell lines. Luciferase gene indicated that miR-1307 directly bound the 3'-UTR of AGAP1. miR-1307 was negatively correlated with AGAP1 in clinical study. miR-1307 could significantly promote the proliferation, migration, and invasion of OS cells. In addition, upregulation of AGAP1 could significantly inhibit the role of miR-1307 in OS. In conclusion, our study suggests that OS cell-derived exosomal miR-1307 promotes the proliferation, migration, and invasion of OS cells via targeting AGAP1, and miR-1307-AGAP1 axis may play an important role in the future treatment of OS.

RGS12 is a novel tumor suppressor in osteosarcoma that inhibits YAP-TEAD1-Ezrin signaling.

Osteosarcoma (OS) is the most common primary malignancy of the bone that predominantly affects children and adolescents. Hippo pathway is a crucial regulator of organ size and tumorigenesis. However, how Hippo pathway regulates the occurrence of osteosarcoma is largely unknown. Here, we reported the regulator of G protein signaling protein 12 (RGS12) is a novel Hippo pathway regulator and tumor suppressor of osteosarcoma. Depletion of Rgs12 promotes osteosarcoma progression and lung metastasis in an orthotopic xenograft mouse model. Our data showed that knockdown of RGS12 upregulates Ezrin expression through promoting the GNA12/13-RhoA-YAP pathway. Moreover, RGS12 negatively regulates the transcriptional activity of YAP/TEAD1 complex through its PDZ domain function to inhibit the expression and function of the osteosarcoma marker Ezrin. PDZ domain peptides of RGS12 can inhibit the development of intratibial tumor and lung metastases. Collectively, this study identifies the RGS12 is a novel tumor suppressor in osteosarcoma through inhibiting YAP-TEAD1-Ezrin signaling pathway and provides a proof of principle that targeting RGS12 may be a therapeutic strategy for osteosarcoma.

Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study

SummaryThe Forteo Patient Registry estimated the incidence of osteosarcoma in US patients treated with teriparatide and enrolled in the study between 2009 and 2019. No incident cases of osteosarcoma were identified among patients registered, and the crude incidence rate was 0 (95% confidence interval [CI], 0–10.2) cases per million person-years.PurposeThe prospective, voluntary Forteo Patient Registry was established to estimate the incidence of osteosarcoma in patients who have received treatment with teriparatide (Forteo).MethodsInformation on US adults prescribed teriparatide and enrolled in the Forteo Patient Registry 2009–2019 was linked with data from participating state cancer registries annually (2010–2019) to identify incident osteosarcoma cases using a standardized linkage algorithm. Teriparatide exposure was ascertained from self-reported data that included teriparatide initiation and demographics necessary to complete linkage. Osteosarcoma cases diagnosed on or after January 1, 2009, were identified by participating state cancer registries. The crude incidence rate (IR) and standardized incidence ratio (SIR) of observed cases to the expected number of cases adjusted to the background rate (3 per million person-years) and corresponding 95% CIs for the occurrence of osteosarcoma were calculated whereby the cumulative amount of person-time observed was adjusted for mortality.ResultsData for 75,247 enrolled patients (representing 361,763 cumulative person-years) were linked to each of 42 participating state cancer registries (covering 93% of the US population), which included information on 6180 cases of osteosarcoma. No matches with incident cases of osteosarcoma following registry enrollment were found. The crude IR was 0 (95% CI, 0–10.2) cases per million person-years and the SIR was 0 (95% CI, 0–3.0).ConclusionsThe ability to draw conclusions about the incidence of osteosarcoma among patients participating in the registry was limited due to the smaller than expected amount of patient follow-up time and the fact that no cases were identified.

Osteosarcoma in a Dachshund: cytological and histopathological aspects

Malignant primary bone neoplasms are characterized by high malignancy and metastatic capacity, commonly affecting dogs of large or giant breeds. The prognosis is reserved to unfavorable for the patients. This paper describes a case of osteosarcoma in the left pelvic limb of a Dachshund, diagnosed by fine-needle aspiration cytology and confirmed by histopathological evaluation. The patient underwent limb amputation and doxorubicin chemotherapy; however, the dog died. This report alerts clinicians to the occurrence of osteosarcoma in small animals and demonstrates the importance of fine-needle aspiration cytology as a tool in the diagnosis of bone neoplasms.

LncRNA NKILA inhibits invasion and migration of osteosarcoma cells via NF-κB/Snail signaling pathway.

Our research explored the possible biological function of long non-coding RNA (lncRNA) NKILA in the pathogenesis of osteosarcoma and its underlying mechanism. NKILA expression in 60 cases of osteosarcoma and adjacent tissues was detected. The correlation between NKILA expression and clinical information was analyzed by Chi-square test. The overexpression plasmid or siRNA of NKILA were transfected into osteosarcoma cells by liposome. Cell proliferation was detected by cell counting kit-8 (CCK-8) assay. Transwell assay was used to check the migratory and invasive abilities. Western Blot was used to detect the expressions of nuclear factor-κB (NF-κB)-related proteins. In addition, we analyzed the cell invasion and migration after treatment of NF-κB inhibitor (JSH) to further verify whether NKILA can participate in the occurrence of osteosarcoma through the NF-κB / Snail signaling pathway. The expression level of NKILA in osteosarcoma tissues was significantly lower than that in adjacent tissues, and was related to tumor size, Enneking stage, and metastasis. After KNKS/NP cells were transfected with NKILA-siRNA, cell proliferation, invasion and migration were enhanced. Transfection of the NKILA overexpression plasmid in Saos2 cells reduced cell proliferation, invasion and migration. NKILA knockdown downregulated the expressions of p65 and E-cadherin, but strikingly increased Snail expression. The RNA binding protein co-immunoprecipitation experiments illustrated that p65 could bind to NKILA. Additionally, JSH was found to reverse the inhibitory effect of NKILA on cell migration and proliferation. NKILA was lowly expressed in osteosarcoma tissues. In addition, high expression of NKILA could suppress the migration and invasion of osteosarcoma cells by inhibiting the NF-κB/Snail signaling pathway.

The expression of Eps15 homology domain 1 is negatively correlated with disease-free survival and overall survival of osteosarcoma patients

BackgroundOsteosarcoma was locally aggressive and frequently metastasizes to the lung. However, the etiology of osteosarcoma was unknown. Thus, exploring the mechanisms behind the occurrence of osteosarcoma was important for its prediction and prevention. To investigate the usefulness of mammalian Eps15 homology domain 1 (EHD1) as a prognostic marker for osteosarcoma, the expression of EHD1 in 57 osteosarcoma patients was measured using immunohistochemistry techniques and correlated with the clinicopathological features of patients.MethodsCorrelations of EHD1 expression levels with clinicopathological features of patients were assessed using the Pearson χ2 test for categorical variables and the Student t test for continuous variables. Cumulative disease-free survival (DFS) curves and overall survival (OS) curves were plotted using the Kaplan–Meier method, and the relationship between each of the variables and survival was assessed by log-rank tests using univariate analysis. Subsequently, the parameters were tested using the multivariate Cox proportional hazards model, which was used to identify independent variables for predicting survival. EHD1 expression [P = 0.020; HR, 5.582; 95% confidence intervals (CI), 1.314–23.72] was an independent prognostic indicator of DFS in osteosarcoma patients; tumor size and EHD1 expression of osteosarcomas were independent prognostic indicators of OS in osteosarcoma patients.ResultsEHD1 protein expression was a positive expression in examined tumor tissues. The median OS time of patients with high expression of EHD1 was 46.8 months (95% CI, 29.8–63.8 months), and the median OS time of patients with low expression of EHD1 was 58.8 months (95% CI, 31.6–86.0 months). The prognosis for patients with low expression of EHD1 in osteosarcomas was significantly better than that for patients with high expression of EHD1 (log-rank test, P = 0.019).ConclusionThe expression of EHD1 was negatively correlated with DFS and OS of osteosarcoma patients; therefore, the expression of EHD1 is a prognostic marker for prediction and prevention of osteosarcomas.

Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway

MicroRNA (miRNA) is known to be involved in regulating the proliferation, migration and apoptosis of cancer cells in osteosarcoma. In this study, We aim to explore the expression of hsa-let-7 g and its role in pathogenesis of osteosarcoma. By analyzing clinical data. We found high expression of hsa-let-7 g in patients with osteosarcoma. The patients with higher expression of hsa-let-7 g showed poorer prognosis and lower survival rate. After downregulation of hsa-let-7 g in cell model and animal model, we found that with downregulation of hsa-let-7 g, the proliferation of osteosarcoma cells was significantly reduced, the level of migration and invasion was down-regulated, the cell cycle was inhibited, and cell apoptosis was increased. Through Dual Luciferase Reporter, immunohistochemistry, western blot and other experiments, it was found that hsa-let-7 g down-regulated HOXB1 gene and activated NF-kB pathway to promote the development of osteosarcoma. In conclusion, hsa-let-7 g is highly expressed in osteosarcoma tissues, and high expression of hsa-let-7 g can promote the occurrence of osteosarcoma by down-regulating HOXB1 and activating NF-kB pathway.

MiR-155 affects osteosarcoma cell proliferation and invasion through regulating NF-κB signaling pathway.

Osteosarcoma can form tumor osteoid tissue and bone tissue directly or indirectly through cartilage stage. It mainly occurs in children and adolescents with high mortality. MicroRNA (miRNA) possesses tissue sensitivity as tumor biomarker and plays a promoting or inhibitory role in tumor pathogenesis as oncogene or tumor suppressor gene. It was found that miR-155 was abnormally expressed in tumor and could be treated as a biomarker for cancer progression. However, miR-155 expression in osteosarcoma and related mechanism still remains unclear. This study aimed to explore the role of miR-155 in osteosarcoma occurrence and development. Osteosarcoma cell line MG-63 was cultured in vitro and transfected by miR-155 mimics or inhibitor. MiR-155 expression was examined by Real-time PCR (RT-PCR). Cell proliferation was evaluated by MTT assay. Caspase 3 activity was determined by caspase 3 activity detection kit. Cell invasion was measured by transwell assay. B-cell lymphoma-2 (Bcl-2) and nuclear factor κB (NF-κB) protein expressions were assessed by Western blot. MiR-155 mimics significantly up-regulated miR-155 expression, promoted MG-63 cell proliferation and invasion, inhibited caspase 3 activity, and up-regulated expressions of NF-κB and Bcl-2 compared with control group (p < 0.05). However, miR-155 inhibitor significantly inhibited MG-63 cell proliferation and invasion, enhanced caspase 3 activity, and reduced expressions of NF-κB and Bcl-2 compared with control group (p < 0.05). MiR-155 affected osteosarcoma cell proliferation and apoptosis through regulating NF-κB signaling pathway, indicating it might be a new biomarker for osteosarcoma diagnosis and treatment.

Emerging Roles of Circular RNAs in Osteosarcoma.

Osteosarcoma (OS) is a primary malignant bone tumor in early adolescence with high metastasis and death rates. Although the combination of polychemotherapy and surgical excision increased the survival rates up to 60%, the prognosis remains poor for most patients with metastatic or recurrent osteosarcoma. However, the exact pathogenic mechanism and pivotal elements regulating tumor invasion and metastasis are largely unknown. Circular RNAs (circRNAs) are novel endogenous non-coding RNA (ncRNA) molecules that generate the cyclic structure from back splicing. An increasing number of studies show that circRNAs can regulate transcriptional or posttranscriptional gene expression by acting as microRNA (miRNA) sponges and are involved in regulation of many important biological processes. The deregulation of some circRNAs was demonstrated in osteosarcoma. Furthermore, some circRNAs were identified to play essential roles in osteosarcoma occurrence, invasion, and metastasis. This review summarizes the regulatory effect of circRNAs in the occurrence and development of osteosarcoma, concentrating on deregulation, regulatory mechanisms, and functions of circRNAs and their potential value as biomarkers and therapy.

Identifying osteosarcoma metastasis associated genes by weighted gene co-expression network analysis (WGCNA).

Osteosarcoma (OS), the most common malignant bone tumor, accounts for the heavy healthy threat in the period of children and adolescents. OS occurrence usually correlates with early metastasis and high death rate. This study aimed to better understand the mechanism of OS metastasis.Based on Gene Expression Omnibus (GEO) database, we downloaded 4 expression profile data sets associated with OS metastasis, and selected differential expressed genes. Weighted gene co-expression network analysis (WGCNA) approach allowed us to investigate the most OS metastasis-correlated module. Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to give annotation of selected OS metastasis-associated genes.We select 897 differential expressed genes from OS metastasis and OS non-metastasis groups. Based on these selected genes, WGCNA further explored 142 genes included in the most OS metastasis-correlated module. Gene Ontology functional and KEGG pathway enrichment analyses showed that significantly OS metastasis-associated genes were involved in pathway correlated with insulin-like growth factor binding.Our research figured out several potential molecules participating in metastasis process and factors acting as biomarker. With this study, we could better explore the mechanism of OS metastasis and further discover more therapy targets.

MiR-155 Affects Osteosarcoma MG-63 Cell Autophagy Induced by Adriamycin Through Regulating PTEN-PI3K/AKT/mTOR Signaling Pathway.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a positive regulatory role on cell autophagy through inhibiting PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. miR-155 plays a critical role in osteosarcoma occurrence and chemoresistance. Bioinformatics analysis revealed the targeted binding site between miR-155 and the 3'-UTR (untranslated region) of PTEN mRNA. This study investigated the role of miR-155 in regulating osteosarcoma cell autophagy, chemosensitivity to Adriamycin (ADM), and PTEN-PI3K/AKT/mTOR signaling pathway. Dual luciferase reporter gene assay confirmed the relationship between miR-155 and PTEN. MG-63 cells and drug-resistant MG-63/ADM cells were treated by ADM to compare miR-155, PTEN, p-AKT, p-mTOR, and Beclin-1 expressions. Cell apoptosis was tested by flow cytometry. MG-63/ADM cells were divided into five groups, including anti-miR-NC, anti-miR-155, pSicoR-blank, pSicoR-PTEN, and anti-miR-155+pSicoR-PTEN group. miR-155 targeted suppressed PTEN expression. miR-155, p-AKT, and p-mTOR significantly increased, while PTEN and Beclin-1 obviously reduced in MG-63/ADM cells compared with MG-63 cells. ADM treatment markedly elevated miR-155, p-AKT, and p-mTOR expressions, whereas reduced PTEN level. Beclin-1 was slightly upregulated, and autophagy and apoptosis levels were low. Anti-miR-155 and/or pSicoR-PTEN significantly enhanced PTEN and Beclin-1 expressions, cell apoptosis, and autophagy induced by ADM and declined p-AKT and p-mTOR levels. miR-155 targeted suppressed PTEN expression, enhanced PI3K/AKT/mTOR signaling pathway, inhibited cell apoptosis and autophagy induced by ADM, and reduced sensitivity to ADM.

Long Noncoding RNA SNHG16 Promotes Cell Proliferation by Sponging MicroRNA-205 and Upregulating ZEB1 Expression in Osteosarcoma

Background/Aims: Long noncoding RNAs (lncRNAs) have been a research hotspot, as they play important roles in tumor development. However, their expression pattern and biological function in osteosarcoma have not yet been clarified. Methods: Differentially expressed lncRNAs in osteosarcoma and paracarcinoma tissues were identified by screening an lncRNA microarray, and candidate lncRNAs were verified by quantitative real-time PCR (qRT-PCR). A series of bioinformatics and molecular biological methods were adopted to investigate the interaction among lncRNA, microRNA (miRNA), and miRNA target genes during the development and occurrence of osteosarcoma. Cell viability was measured using a Cell Counting Kit-8 assay. Results: Chip microarray screening combined with the validation of differentially expressed candidate lncRNAs showed that the lncRNA small nucleolar RNA host gene 16 (SNHG16) had the largest fold change. SNHG16 was highly expressed in osteosarcoma tissues and cell lines, and its downregulation led to the suppressed proliferation of osteosarcoma cells. Further investigations revealed that SNHG16 could upregulate zinc finger E-box-binding homeobox 1 (ZEB1) expression by acting as an endogenous sponge of miR-205. Moreover, rescue assays proved that the effects of SNHG16 on the proliferation of osteosarcoma cells were dependent on miR-205. Conclusion: SNHG16 can significantly enhance the proliferation of osteosarcoma cells. In addition, SNHG16, miR-205, and ZEB1 interact in a common pathway during the development and occurrence of osteosarcoma, providing novel targets for intervention in the treatment of osteosarcoma.

Myokines related to leukocyte recruitment are down-regulated in osteosarcoma.

Myokines are cytokines that are secreted by muscle cells during exercises, muscle development and pathology. Studies have shown that expression of some individual myokines was altered in tumors. However, comprehensive analyses of myokines' expression in osteosarcoma (OS), the most common malignant tumor in musculoskeletal system, have not been performed. In this study, we analyzed the expression of 35 myokines in osteosarcoma, peritumoral skeletal muscle, and cancellous bone by qRT-PCR. Heatmap analysis based on the expression pattern of these myokines revealed that OS is more likely derived from cancellous bone than peritumoral skeletal muscle. Thus, we compared the expression of myokines between OS and cancellous bone to reveal a potential role of myokines in OS development. Our results showed that expression of 19 myokines in OS was significantly lower than that in cancellous bone. KEGG signaling pathway analysis showed that these 19 myokines are involved in several important signaling pathways, one of which was associated with leukocyte recruitment in TNF-α signaling. We verified that expression of these leukocyte recruitment-related myokines were down-regulated in OS cell line MNNG compared to those in human BMSC. Downregulation of the myokines related to leukocyte recruitment suggests that escaping from host immune system may help the occurrence of osteosarcoma.