UCA1 Inhibits NKG2D-mediated Cytotoxicity of NK Cells to Breast Cancer.

BACKGROUND: Natural killer cells play important roles in tumor immune surveillance, and cancer cells must resist this surveillance in order to progress and metastasise. INTRODUCTION: The study aimed to explore the mechanism of how breast cancer cells become resistant to the cytotoxicity of NK cells. METHODS: We established NK-resistant breast cancer cells by exposing MDA-MB-231 cells and MCF-7 cells to NK92 cells. Profiles of lncRNA were compared between the NK-resistant and parental cell lines. Primary NK cells were isolated by MACS, and the NK attacking effect was tested by non-radioactive cytotoxicity. The change in lncRNAs was analyzed by Gene-chip. The interaction between lncRNA and miRNA was displayed by Luciferase assay. The regulation of the gene was verified by QRT-PCR and WB. The clinical indicators were detected by ISH, IH, and ELISA, respectively. RESULTS: UCA1 was found to be significantly up-regulated in both NK-resistant cell lines, and we confirmed such up-regulation on its own to be sufficient to render parental cell lines resistant to NK92 cells. We found that UCA1 up-regulated ULBP2 via the transcription factor CREB1, while it up-regulated ADAM17 by "sponging" the miR-26b-5p. ADAM17 facilitated the shedding of soluble ULBP2 from the surface of breast cancer cells, rendering them resistant to killing by NK cells. UCA1, ADAM17, and ULBP2 were found to be expressed at higher levels in bone metastases of breast cancer than in primary tumors. CONCLUSION: Our data strongly suggest that UCA1 up-regulates ULBP2 expression and shedding, rendering breast cancer cells resistant to killing by NK cells.

Solute carrier family 35 member A2 regulates mitophagy through the PI3K/AKT/mTOR axis, promoting the proliferation, migration, and invasion of osteosarcoma cells.

The treatment of osteosarcoma patients exhibits individual variability, underscoring the critical importance of targeted therapy. Although (Solute carrier family 35 member A2) SLC35A2's role in the progression of various cancers has been extensively investigated, its specific implications in osteosarcoma remain unexplored. Leveraging data from the (The Cancer Genome Atlas) TCGA and (Genotype-Tissue Expression) GTEx databases, we have discerned that SLC35A2 is notably upregulated in osteosarcoma and correlates with the prognosis of osteosarcoma patients. Consequently, it becomes imperative to delve into the role of SLC35A2 in the context of osteosarcoma. Our research substantiates that SLC35A2 exerts a notable influence on mitochondrial autophagy in osteosarcoma, thereby exerting cascading effects on the proliferation, migration, invasion, and apoptosis of osteosarcoma cells. Mechanistically, SLC35A2 orchestrates mitochondrial autophagy via the PI3K/AKT/mTOR signaling pathway. Moreover, we have conducted rigorous animal experiments to further corroborate the repercussions of SLC35A2 on osteosarcoma growth. In summation, our study elucidates that SLC35A2's modulation of mitochondrial autophagy through the PI3K/AKT/mTOR signaling pathway constitutes a pivotal factor in the malignant progression of osteosarcoma, unveiling promising therapeutic targets for patients grappling with this condition.

LncRNA LBX2-AS1 impacts osteosarcoma sensitivity to JQ-1 by sequestering miR-597-3p away from BRD4.

Objective: Recent knowledge concerning the significance of long non-coding RNA (lncRNA)-mediated ceRNA networks provides new insight into their possible roles as specific biomarkers for the treatment of osteosarcoma (OS). Thus, this study aims to clarify the functional relevance and mechanistic actions of lncRNA LBX2-AS1 in OS. Methods: Differential analysis was performed by integrating the TCGA and GTEx databases. Cox regression analysis was then employed to assess the prognostic value of the model. The expression of lncRNA LBX2-AS1 and miR-597-3p was quantified in OS cell lines by qRT-PCR. The proliferation, migration, invasion, and apoptosis of OS cell lines in response to manipulated lncRNA LBX2-AS1 were evaluated by MTT, colony formation, transwell, Western blot, and flow cytometry assays. Luciferase activity was assayed to validate the reciprocal regulation between lncRNA LBX2-AS1 and miR-597-3p. The protein levels of BRD4 and EMT-related factors were examined by Western blot assay. Finally, tumor growth in response to LBX2-AS1 knockdown was evaluated in xenograft-bearing nude mice. Results: By integrating the GTEx and TCGA databases, we identified 153 differentially expressed lncRNAs. Among them, 5 lncRNAs, RP11-535M15.1, AC002398.12, RP3-355L5.4, LBX2-AS1, and RP11.47A8.5, were selected to establish a model, which predicted the prognosis of OS. Higher lncRNA LBX2-AS1 expression was noted in OS tissues relative to that in normal tissues. Silencing lncRNA LBX2-AS1 facilitated apoptosis and curtailed proliferative, migratory, and invasive capacities of OS cells. Mechanistically, lncRNA LBX2-AS1 could elevate the expression of BRD4, an oncogene, by competitively binding to miR-597-3p. More importantly, knockdown of lncRNA LBX2-AS1 increased the sensitivity of OS cells to the BRD4 inhibitor JQ-1. Finally, the tumor growth of OS cell xenografts was constrained in vivo in the presence of lncRNA LBX2-AS1 knockdown. Conclusion: In conclusion, lncRNA LBX2-AS1 promotes the growth of OS and represses the sensitivity to JQ-1 by sponging miR-597-3p to elevate the expression of BRD4.

FKBP11 improves the malignant property of osteosarcoma cells and acts as a prognostic factor of osteosarcoma.

BACKGROUND: Osteosarcoma has become the most common bone malignancy in adolescents. Although the clinical treatment of osteosarcoma has advanced considerably in recent years, the 5-year survival rate has not improved significantly. Recently, many studies have shown that mRNA has unique advantages as a target for drug therapy. Therefore, this study aimed to identify a new prognostic factor and provide a new target for the treatment of osteosarcoma to improve the prognosis of patients. METHODS AND RESULTS: We selected prognostic genes that are closely associated with osteosarcoma clinical features by obtaining osteosarcoma patient information from the GTEx and TARGET databases, and then we developed a risk model. We detected the expression of FKBP11 in osteosarcoma by qRT-PCR, western blotting, and immunohistochemistry and performed CCK-8, Transwell, colony formation, and flow cytometry assays to reveal the regulatory role of FKBP11. We found that FKBP11 was highly expressed in osteosarcoma; silencing FKBP11 expression suppressed the invasion and migration of osteosarcoma cells, slowed cell proliferation, and promoted apoptosis. We also found that silencing the expression of FKBP11 led to inhibition of MEK/ERK phosphorylation. CONCLUSIONS: In conclusion, we validated that the prognostic factor FKBP11 is closely associated with osteosarcoma. Additionally, we identified a novel mechanism by which FKBP11 ameliorates the malignant properties of osteosarcoma cells through the MAPK pathway and serves as a prognostic factor in osteosarcoma. This study provides a new method for the treatment of osteosarcoma.

Stabilization of SAMHD1 by NONO is crucial for Ara-C resistance in AML.

Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be elevated in Ara-C-resistant AML patients and to play a crucial role in mediating Ara-C resistance in AML. However, the mechanism by which SAMHD1 is upregulated in resistant AML remains unknown. In this study, NONO interacted with and stabilized SAMHD1 by inhibiting DCAF1-mediated ubiquitination/degradation of SAMHD1. Overexpression of NONO increased SAMHD1 expression and reduced the sensitivity of AML cells to Ara-C, and downregulation of NONO had the opposite effects. In addition, the DNA-damaging agents DDP and adriamycin (ADM) reduced NONO/SAMHD1 expression and sensitized AML cells to Ara-C. More importantly, NONO was upregulated in Ara-C-resistant AML cells, resulting in increased SAMHD1 expression in resistant AML cells, and DDP and ADM treatment resensitized resistant AML cells to Ara-C. This study revealed the mechanism by which SAMHD1 is upregulated in Ara-C-resistant AML cells and provided novel therapeutic strategies for Ara-C-resistant AML.

The synergistic anticancer effect of the bromodomain inhibitor OTX015 and histone deacetylase 6 inhibitor WT-161 in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. METHODS: Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. RESULTS: The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of ß-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. CONCLUSIONS: Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

Serglycin promotes proliferation, migration, and invasion via the JAK/STAT signaling pathway in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a common disease in the world, and its pathogenesis is still unclear. This study aims to identify the key genes that promote the proliferation, invasion, and metastasis of osteosarcoma cells. METHOD: GSE124768 and GSE126209 were downloaded from the Gene Expression Omnibus (GEO) database. The gene ontology and enrichment pathway were analyzed by FunRich software. qPCR and Western blot were used to detect the gene expression. After gene knockdown, Transwell and wound healing assays were conducted on osteosarcoma cells to detect whether the genes were defined before enhancing the invasion of osteosarcoma. RESULTS: Totally, 341 mRNAs were found to be regulated differentially in osteosarcoma cells compared to osteoblasts. In addition, the expression level of Serglycin (SRGN) in osteosarcoma cells was higher than that in human osteoblasts. The invasion and proliferation ability of osteosarcoma cells with upregulated Serglycin was significantly increased, and on the contrary, decreased after Serglycin knockdown. Moreover, we preliminarily found that Serglycin may associate with the JAK/STAT signaling pathway. CONCLUSIONS: By using microarray and bioinformatics analyses, differently expressed mRNAs were identified and a complete gene network was constructed. To our knowledge, we describe for the first time Serglycin as a potential biomarker.

Targeting the p300/NONO axis sensitizes melanoma cells to BRAF inhibitors.

BRAF inhibitors (BRAFi) that target BRAF V600E kinase, a driver mutation found in 50% of melanomas, show a significant antitumor response, but the common emergence of acquired resistance remains a challenge. Abnormal expression of RAF isoforms CRAF and ARAF reactivates pERK1/2, which plays crucial roles in the acquisition of resistance of melanoma cells. However, the mechanisms of dysregulation of RAF isoforms in resistant melanoma cells remain unknown. Here, we identified NONO interacted with and stabilized both CRAF and ARAF in melanoma cells, and that NONO was acetylated at 198K by p300 acetyltransferase, which stabilized NONO via antagonizing its ubiquitination/degradation mediated by RNF8. The upregulation of both p300 and NONO promoted the rebound of pERK1/2 and the subsequent resistance of melanoma cells to BRAFi, and the activation of ERK1/2 in turn induced p300 to form a positive feedback loop in resistant melanoma cells. There was a positive correlation between p300 and NONO in resistant melanoma cells and clinical samples, and p300 inhibitor C646 overcame the resistance of resistant melanoma cells to BRAF inhibitors in vitro and in vivo. Our findings reveal that targeting the positive feedback loop of p300-NONO-CRAF/ARAF-pERK1/2 may be excellent strategies to overcome the resistance of BRAF inhibitors for melanoma patients.

Role of LncRNAs in regulating cancer amino acid metabolism.

The metabolic change of tumor cells is an extremely complicated process that involves the intersection and integration of various signal pathways. Compared with normal tissues, cancer cells show distinguished metabolic characteristics called metabolic reprogramming, which has been considered as a sign of cancer occurrence. With the deepening of tumor research in recent years, people gradually found that amino acid metabolism played crucial roles in cancer progression. Long non-coding RNAs (lncRNAs), which are implicated in many important biological processes, were firstly discovered dysregulating in cancer tissues and participating in extensive regulation of tumorigenesis. This review focuses on the reprogramming of amino acid metabolism in cancers and how lncRNAs participate in the regulatory network by interacting with other macromolecular substances. Understanding the functions of lncRNA in amino acid reprogramming in tumors might provide a new vision on the mechanisms of tumorigenesis and the development of new approaches for cancer therapy.

HDAC6 inhibitor WT161 performs anti-tumor effect on osteosarcoma and synergistically interacts with 5-FU.

BACKGROUND: WT161, as a selective HDAC6 inhibitor, has been shown to play anti-tumor effects on several kinds of cancers. The aim of the present study is to explore the roles of WT161 in osteosarcoma and its underlying mechanisms. METHODS: The anti-proliferative effect of WT161 on osteosarcoma cells was examined using MTT assay and colony formation assay. Cell apoptosis was analyzed using flow cytometer. The synergistic effect was evaluated by isobologram analysis using CompuSyn software. The osteosarcoma xenograft models were established to evaluate the anti-proliferative effect of WT161 in vivo. RESULTS: WT161 suppressed the cell growth and induced apoptosis of osteosarcoma cells in a dose- and time-dependent manner. Mechanistically, we found that WT161 treatment obviously increased the protein level of PTEN and decreased the phosphorylation level of protein kinase-B (AKT). More importantly, WT161 showed synergistic inhibition with 5-FU on osteosarcoma cells in vitro and in vivo. CONCLUSIONS: These results indicate that WT161 inhibits the growth of osteosarcoma through PTEN and has a synergistic efficiency with 5-FU.

The novel prognostic risk factor STC2 can regulate the occurrence and progression of osteosarcoma via the glycolytic pathway.

Osteosarcoma, a highly aggressive malignant tumor of the bone, usually occurs in children and young adults. However, although the considerable achievement in the clinical treatment of osteosarcoma recent years, the overall survival of osteosarcoma patients has not been obviously improved. Cancer cells preferentially use glycolysis instead of oxidative phosphorylation to meet their increased energetic and biosynthetic demands, a phenomenon known as the Warburg effect. Glycolysis is a driving factor in multiple cancers and is emerging as a new cancer target treatment. In the present study, we established a model to screen for glycolysis-associated genes in osteosarcoma. This risk score of the model were correlated with clinical characteristics osteosarcoma patients. Besides, a functional assay identified that STC2 enhanced the glycolysis of osteosarcoma cells. Modulation of STC2 changes glucose consumption and lactate production as well as GLUT1 expression in osteosarcoma. Furthermore, we identified that change in the expression levels of STC2 affected the proliferation, invasion, and migration of osteosarcoma cells. Our findings showed STC2 as a new tumor-promoting factor of osteosarcoma cells through enhancing glycolysis.

LncRNA GSEC promotes the proliferation, migration and invasion by sponging miR-588/ EIF5A2 axis in osteosarcoma.

BACKGROUND: Long noncoding RNAs (LncRNAs) show dysregulation in a variety of cancers. However, the function and specific mechanism of LncRNA GSEC in the progression of osteosarcoma remain mostly unknown. In this study, we sought to elucidate the role and mechanism of LncRNA GSEC in the occurrence and progression of osteosarcoma. METHODS: we examined the expression of LncRNA GSEC in osteosarcoma cell lines by quantitative real time PCR. In vitro experiments, including transwell assays, cck8 assays, and flow cytometry analysis have biologically demonstrated the effect of LncRNA GSEC on the proliferation and migration of osteosarcoma cell lines. Furthermore, the regulation of miR-588 by LncRNA GSEC was determined by luciferase reporter assay and quantitative real time PCR. What's more, subcutaneous tumor formation was performed in nude mice to monitor the growth of the tumor in vivo. RESULTS: We found that the expression of LncRNA GSEC was up-regulated in osteosarcoma cell lines. Overexpression of LncRNA GSEC promoted the proliferating and migratory capacity, and inhibited the apoptosis of osteosarcoma cells. Conversely, knockdown of LncRNA GSEC resulted in the opposite effect. Mechanistically, we identified LncRNA GSEC functioned as the sponge of miR-588, thus inhibiting the miR-588/EIF5A2 signal pathway. In addition, the expression of miR-588 was negatively correlated with LncRNA GSEC, and the effect by silencing or overexpressing LncRNA GSEC could be rescued by the introduction of miR-588 mimics or inhibitors, respectively. CONCLUSIONS: In summary, this study shows that LncRNA GSEC promotes the proliferation and invasion of OS through the regulation of miR-588/EIF5A2 pathway, which might provide a new strategy for the treatment of osteosarcoma in the future.

Identification of CDC5L as bridge gene between chronic obstructive pulmonary disease and lung adenocarcinoma.

Aim: This study aimed to explore the genetic and epigenetic similarities between chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD). Materials & methods: We mainly used Weighted correlation network analysis, protein-protein interaction network and pivot analysis to identify hub modules, bridge regulators, bridge genes and hub-driving genes in both diseases and carried out verifying using external datasets. Results: We identified eight bridge regulators, 19 key molecules in the COPD model and ten key molecules in the LUAD model. Moreover, we validated that CDC5L could be a reliable biomarker in COPD and may regulate cell proliferation and metastasis in LUAD via promoter methylation. Conclusion: Our results might form a theoretical foundation for future study at an epigenetic level.

Identification of BRMS1L as Metastasis Suppressing Gene in Esophageal Squamous Cell Carcinoma.

INTRODUCTION: Breast cancer metastasis suppressor 1 like (BRMS1-like)was first reported to be a component of the Sin3-HDAC complex, but the role in the progression of cancers was largely unknown. Our previous study reported that BRMS1L promoted the metastasis of breast cancer through facilitating the recruitment of HDAC complex to the promoter FZD10, and hence suppressing the transcription of FZD10. METHODS: In this study, we detected the expression level of BRMS1L in esophageal squamous cell carcinoma (ESCC). The effect of BRMS1L in TE-1D (knockdown) and ECA-109 (overexpression) cell lines was explored by transwell assays, wound healing assays, and cell adhesion assays. Quantitative real­time PCR, Western blot analysis, and luciferase assays were used to detect the interaction of the CBP/P300-BRMS1L-ITGA7 axis. RESULTS: In the present study, we found that knockdown of BRMS1L promoted the migration, invasion, and epithelial-mesenchymal transition (EMT). Conversely, overexpression of BRMS1L inhibited the migration and invasion of ESCC. Mechanistically, BRMS1L exerted their metastasis-suppressing role via transcriptionally repress ITGA7 expression. Moreover, we revealed that CBP/p 300 regulated the expression of BRMS1L and might be responsible for the down-regulation of BRMS1L in ESCC. CONCLUSION: Collectively, we identified the role of CBP/p300-BRMS1L-ITGA7 axis in the metastasis of ESCC.

Exosomes May Be the Potential New Direction of Research in Osteoarthritis Management.

Osteoarthritis (OA) is a joint degenerative disease, which is prominent in the middle-aged and elderly population, often leading to repeated pain in the joints of patients and seriously affecting the life quality of patients. At present, the treatment of OA mainly depends on the surgery and drug treatment. Nevertheless, these treatments still face many problems, such as surgical safety, complications, and drug side effects. Exosomes can be secreted and released by multiple cell types and have lipid bilayer membranes and contain abundant biological molecules, including proteins, lipids, and nucleic acids. Moreover, exosomes play a critical role in local and distal intercellular and intracellular communication. In recent years, several studies have found that exosomes can regulate the progression of OA and have a potential efficacy for OA treatment. Thus, in this article, we summarize and review the relevant research of exosomes in OA and emphasize the importance of exosomes in the development of OA.

Mesenchymal stem cell-associated lncRNA in osteogenic differentiation.

Mesenchymal stem cells (MSCs) have the ability to differentiate into multiple cell types, including osteogenic, chondrogenic and adipogenic lineages. Osteogenic differentiation of MSCs plays a critical role in bone tissue engineering. Inducing MSC osteogenesis represents a potential treatment that promotes bone formation and bone regeneration. Recently, long non-coding RNA (lncRNA) was shown to participate in the occurrence and development of various diseases. Different lncRNA expression patterns can regulate the cell cycle, proliferation, metastasis, immunobiology and differentiation. With the recent extensive study of lncRNAs, an increasing number of lncRNAs are being studied in the MSC field. Furthermore, some lncRNAs have been confirmed to regulate MSC osteogenesis. Therefore, here, we review research concerning lncRNA in osteogenic differentiation of MSCs and highlight the importance of lncRNA in bone formation and bone regeneration.

HDAC6 inhibitor WT161 induces apoptosis in retinoblastoma cells and synergistically interacts with cisplatin.

BACKGROUND: WT161 is a recently discovered histone deacetylase 6 (HDAC6) inhibitor which shows anti-tumor effects on multiple myelomas and breast cancer. However, the role of WT161 in retinoblastoma remains unclear. The aim of this study is to explore the role of WT161 in retinoblastoma and its underlying mechanisms. METHODS: The anti-proliferation of WT161 on retinoblastoma cells was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and soft agar colony formation assay. Cell apoptosis was analyzed using flow cytometer. WT161 and DDP synergistic effect was evaluated by isobologram analysis using CompuSyn software. RESULTS: WT161 suppressed the cell growth and induced apoptosis of retinoblastoma cells in a dose- and time-dependent manner. Mechanistically, WT161 increases the transcription of Bad through activating Bad promoter. Chromatin immunoprecipitation (ChIP) assay showed WT161 treatment increased acetylated histone H3 (AcH3) and acetylated histone H4 (AcH4) on the Bad promoter in retinoblastoma cells. In addition, WT161 shows synergistically inhibitory effects on retinoblastoma cell combined with cisplatin. CONCLUSIONS: These results indicate that WT161, as a selective HDAC6 inhibitor, is a promising agent against retinoblastoma.

Macrophage-derived CCL18 promotes osteosarcoma proliferation and migration by upregulating the expression of UCA1.

Osteosarcoma (OS), which is the most common primary malignant bone tumor, has a high incidence of pulmonary metastasis. CCL18 (C-C motif chemokine ligand 18), which is secreted by tumor-associated macrophages (TAMs), has been found to be increased in various tumors and is associated with tumor metastasis. However, the role of CCL18 in OS remains unclear. Here, we evaluated the effect of CCL18 on the OS cell lines MG63 and 143B and explored its potential mechanisms. We found that CCL18 enhanced the proliferation and migration of OS cells and upregulated UCA1 through transcription factor EP300. Subsequently, we further revealed that the downstream Wnt/ß-catenin signaling pathway participated in this process. In addition, the high expression of CCL18 in both tissue and serum from patients was closely related to pulmonary metastasis and poor survival in OS patients. The tumor xenograft models also showed that CCL18 promoted the metastasis of OS cells. Collectively, our study indicated that macrophage-derived CCL18 promotes OS proliferation and metastasis via the EP300/UCA1/Wnt/ß-catenin pathway and that CCL18 may be used as a prognostic marker and therapeutic target of OS. KEY MESSAGES: CCL18 promotes proliferation and migration of osteosarcoma cells by EP300/ UCA1/ Wnt/ß-catenin pathway. CCL18+ TAMs are significantly correlated with pulmonary metastasis and poor survival in osteosarcoma patients. CCL18 may be used as a prognostic marker and therapeutic target for osteosarcoma.

LncRNA SNHG5 promotes the progression of osteosarcoma by sponging the miR-212-3p/SGK3 axis.

BACKGROUND: Long non-coding RNA (lncRNA) SNHG5 has been found to play an important role in tumors. Nevertheless, the function and mechanism of lncRNA SNHG5 in osteosarcoma (OS) remains unclear. The purpose of this study was to investigate whether lncRNA SNHG5 can regulate the occurrence and development of OS cells. METHODS: We performed quantitative real time PCR to detect the expression of lncRNA SNHG5 in OS cells. 143B, MG63 (knockdown) and U2OS, U2R (overexpression) cell lines were chosen for the function study of SNHG5. The effect of SNHG5, miR-212-3p, and SGK3 in OS cells was explored by MTT assays, clony formation, flow cytometry, transwell assays, wound healing assays, and cell spreading assays. Quantitative real-time PCR, Western blot analysis and luciferase assays were used to detect the interaction between lncRNA SNHG5 and miR-212-3p. RESULTS: In this study, knockdown of lncRNA SNHG5 suppressed the growth and metastasis of OS cells, whereas the overexpression of SNHG5 produced an opposite result. Mechanistically, lncRNA SNHG5 functions as a sponger against miR-212-3p and suppresses the miR-212-3p/SGK3 signaling pathway. Introduction of miR-212-3p mimics or inhibitors reverses SNHG5 overexpression or silences the exerted tumor promoting or suppressing effect. In addition, our results showed that the function of SNHG5 can be rescued by miR-212-3p and can regulate the growth and metastasis of OS cells via SGK3, the downstream target of miR-212-3p. CONCLUSIONS: In summary, our study demonstrated that lncRNA SNHG5 can regulate the proliferation and metastasis of OS cells through the miR-212-3p/SGK3 axis. This axis may provide a new target for future clinical treatment.