Invasion Of Osteosarcoma Cells Research Articles

<p>Long Noncoding RNA LINC00839 Promotes the Malignant Progression of Osteosarcoma by Competitively Binding to MicroRNA-454-3p and Consequently Increasing c-Met Expression</p>

PurposeThis study was conducted to determine the expression and prognostic relevance of long intergenic non-protein coding RNA 839 (LINC00839) in osteosarcoma (OS) and to explore the detailed roles of LINC00839 in regulating OS cell activities and the mechanisms responsible for its cancer-promoting activity in OS.MethodsThe expression of LINC00839 in OS tissues and cell lines was determined by quantitative reverse transcription–polymerase chain reaction. After LINC00839 knockdown, cell counting kit-8 assay, flow cytometric analysis, transwell migration and invasion assay, and in vivo tumor xenograft assay were used to detect its effects on cellular processes in OS. Bioinformatics analyses were conducted to predict the putative miRNAs that target LINC00839. RNA immunoprecipitation assay, luciferase reporter assay, Western blotting analysis, and rescue assays were conducted to establish a relationship among LINC00839, microRNA-454-3p (miR-454-3p), and cellular mesenchymal to epithelial transition factor (c-Met) in OS.ResultsLINC00839 was upregulated in OS tissues and cell lines. OS patients characterized with high LINC00839 expression exhibited shorter overall survival than patients with low LINC00839 expression. LINC00839 knockdown caused a significant reduction in OS cell proliferation, migration, and invasion in vitro. Furthermore, LINC00839 depletion inhibited OS tumor growth in vivo and induced apoptosis. Mechanistically, LINC00839 functions as a competitive endogenous RNA in OS by sponging miR-454-3p. c-Met was confirmed as a direct target gene for miR-454-3p in OS cells and was positively regulated by LINC00839 by competitively binding to miR-454-3p.ConclusionLINC00839 promoted the oncogenicity of OS by targeting the miR-454-3p/c-Met axis. The LINC00839/miR-454-3p/c-Met network may represent a potential target for OS therapy.

RETRACTED: The Sp1/FOXC1/HOTTIP/LATS2/YAP/β‐catenin cascade promotes malignant and metastatic progression of osteosarcoma

The prognosis for osteosarcoma (OS) is dismal due to the aggressive tumor growth and high incidence of metastasis. The long noncoding RNA human homeobox A transcript at the distal tip (HOTTIP) and the transcription factor forkhead box C1 (FOXC1) present oncogenic activities in OS. Here, we aimed at gaining insights into the underlying mechanisms and their crosstalk. The expression of FOXC1 and HOTTIP in OS tissues or cell lines was examined by real-time PCR (RT-PCR) and western blot. The invitro effects of FOXC1 or HOTTIP on cell viability, proliferation, migration, invasion, and expression of target genes were examined using MTT, colony-forming assay, wound-healing, Transwell invasion, and western blot, respectively; the invivo effects were examined using xenograft and experimental metastasis models. Molecular control of HOTTIP on large tumor suppressor 2 (LATS2) or transactivation of FOXC1 or Sp1 on HOTTIP was assessed by combining RNA immunoprecipitation, qRT-PCR, western blot, ChIP, and luciferase assay. Both FOXC1 and HOTTIP were potently up-regulated in OS tissues and cell lines. FOXC1 and HOTTIP essentially maintained viability, proliferation, migration, and invasion of OS cells invitro and contributed to xenograft growth or lung metastasis invivo. Mechanistically, HOTTIP recruited enhancer of zeste homolog 2 (EZH2) and lysine-specific demethylase 1 (LSD1) to silence LATS2 and thus activated YAP/β-catenin signaling. Upstream, Sp1 activated FOXC1 and they both directly transactivated HOTTIP. In summary, we showed that the Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade presented oncogenic activities in OS cells. Targeting FOXC1 or HOTTIP may therefore prove beneficial for OS treatment.

Retraction Statement.

Retraction Statement.

MiR-16-5p Suppresses Progression and Invasion of Osteosarcoma via Targeting at Smad3.

BackgroundMicroRNAs are known to regulate carcinogenesis of osteosarcoma. Although, miR-16-5p is known to exert inhibitory effects on several forms of cancers, its effects on the growth and invasion of osteosarcoma have not been studied.MethodsWe collected human osteosarcoma specimens and adjacent tissues to detect the expression of miR-16-5p by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. The proliferation, migration, and invasion of MG63 and HOS cells following miR-16-5p overexpression and inhibition were detected with cell counting kit-8, wound healing assay, and Transwell assay, respectively. An expression vector carrying a mutated 3′-untranslated region of mothers against decapentaplegic homolog 3 (Smad3) was constructed.ResultsThe results showed that miR-16-5p expression was downregulated in osteosarcoma tissues and cells as compared with adjacent counterparts, while Smad3 was overexpressed in osteosarcoma cells. The overexpression of miR-16-5p resulted in the inhibition of the proliferation, migration, and invasion of osteosarcoma cells and enhanced the therapeutic effect of cisplatin. These effects were attenuated with miR-16-5p expression inhibition. In cells transfected with miR-16-5p mimic, Smad3 expression decreased, while this effect was absent in the cells carrying mutated Smad3.ConclusionsTherefore, miR-16-5p inhibits the growth and invasion of osteosarcoma by targeting Smad3.

Circ0085539 Promotes Osteosarcoma Progression by Suppressing miR-526b-5p and PHLDA1 Axis.

Background: We have previously found that circ0085539/miR-526b-5p axis participated in the progression of osteosarcoma (OS). We have been interested in expanding the networking involving circ0085539 and miR-526-5p. We identified another critical downstream target of this axis, pleckstrin homology-like domain family A member 1 (PHLDA1), thus intending to uncover the interaction between the axis and PHLDA1.Methods: Live imaging of mice tumor xenografts was conducted. Immunohistochemistry (IHC) and H&E staining were performed for our in vivo experiment, while the CCK-8 assay, flow cytometry, wound healing, Transwell invasion, and clone formation were employed to assess cellular biological functions.Results: Circ0085539 was first found to be upregulated in osteosarcoma tissues and cell lines, and circ0085539 knockdown obviously suppressed proliferation and induced apoptosis. Subsequently, miR-526b-5p functionally attenuated the tumor suppressive effects induced by circ0106714 silencing on OS cells. PHLDA1 silencing significantly led to proliferation suppression, apoptosis induction, as well as the inhibition of migration, invasion, and colony formation capabilities in OS cells, which also could be restored by the miR-526b-5p inhibitor.Conclusion: Taken together, circ0085539 effectively promoted progression of osteosarcoma through sponging miR-526b-5p to release PHLDA1, strongly suggesting that in vivo intervention of circ0085539–miR-526b-5p–PHLDA1 axis could function as a promising OS-targeted therapy.

N6-Methyladenosine modification of the TRIM7 positively regulates tumorigenesis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.

BackgroundMetastasis is the leading cause of death in patients with osteosarcoma. Some of these patients fail to respond to chemotherapy and die of metastasis within a short period. Therefore, it is important to identify novel biomarkers to improve the diagnosis and treatment of osteosarcoma. TRIM7 is a member of the tripartite motif (TRIM) family protein that is involved in various pathological conditions including cancer; however, its role in osteosarcoma remains elusive.MethodsCell proliferation, invasion and migration were measured by CCK-8 and Transwell. Immunoprecipitation and mass spectrometry analysis were used to identify candidate proteins associated with TRIM7. Immunoprecipitation, immunofluorescence, pull down and ubiquitination assay were performed to examine the regulation between TRIM7 and its candidate protein. m6A modification of TRIM7 was measured by RNA immunoprecipitation.FindingsTRIM7 expression was upregulated in osteosarcoma tissues and was an independent risk factor in predicting poor prognosis. TRIM7 regulates osteosarcoma cell migration and invasion through ubiquitination of breast cancer metastasis suppressor 1 (BRMS1). Moreover, chemoresistance was readily observed in osteosarcoma cells and in patient-derived xenograft (PDX) mice with higher TRIM7 levels. Loss of TRIM7 m6A modification was observed in osteosarcoma tissues. METTL3 and YTHDF2 were the main factors involved in the aberrant m6A modification of TRIM7.InterpretationOverall, our findings show that TRIM7 plays a key role in regulating metastasis and chemoresistance in osteosarcoma through ubiquitination of BRMS1.FundingThis work was financially supported by grants of NSFC (81001192, 81672658 and 81972521) and National Key Research Project of Science and Technology Ministry (2016YFC0106204).

Expression of concern: MicroRNA-379 inhibits the proliferation, migration and invasion of human osteosarcoma cells by targeting EIF4G2.

The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates.

Long non-coding RNA PGM5-AS1 promotes epithelial-mesenchymal transition, invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition.

Osteosarcoma is an uncommon tumor occurring in bone, accompanied by elevated incidence and reduced rate of healing. Epithelial‐to‐mesenchymal transition (EMT) serves as a conceptual paradigm to explain the invasion and metastasis of osteosarcoma and other cancers. Hence, developing effective therapeutic strategy to treat the EMT of osteosarcoma is essential. Here, we identified the molecular mechanism of long noncoding RNA (lncRNA) PGM5‐AS1 in EMT and progression of osteosarcoma. Microarray‐based analysis was employed to screen the osteosarcoma‐related differentially expressed lncRNAs. The levels of PGM5‐AS1 as well as microRNA‐140‐5p (miR‐140‐5p) and fibrillin‐1 (FBN1) in osteosarcoma tissues and cells were determined. Dual‐luciferase reporter gene assay, RNA pull‐down assay, and RNA immunoprecipitation assay were conducted to validate the relationship among PGM5‐AS1, miR‐140‐5p, and FBN1. Expression of PGM5‐AS1, miR‐140‐5p, and FBN1 was altered by overexpression, shRNA, mimic, or inhibitors in order to investigate how they regulated migration, invasion, and EMT of osteosarcoma cells in vitro. Loss‐ and gain‐of‐function approaches were employed in nude mice to detect their roles in tumorigenesis in vivo. Osteosarcoma tissues and cells exhibited low expression of miR‐140‐5p, but high expression of PGM5‐AS1 and FBN1. PGM5‐AS1 competitively bound to miR‐140‐5p to upregulate FBN1. Furthermore, hindering PGM5‐AS1 and FBN1 or overexpressing miR‐140‐5p dampened migration, invasion, and EMT of osteosarcoma cells in vitro. Furthermore, silencing PGM5‐AS1 or FBN1, or overexpressing miR‐140‐5p markedly inhibited tumorigenesis in nude mice in vivo. Taken together, PGM5‐AS1 depletion causes FBN1 reduction to retard osteosarcoma processes by negatively modulating miR‐140‐5p.

Circ_0010220-mediated miR-503-5p/CDCA4 axis contributes to osteosarcoma progression tumorigenesis.

CircRNAs are reported to exert a significant role in modulating genes in cancers, including osteosarcoma progression. Up to now, the function of circ_0010220 in osteosarcoma is still poorly known. The aim of our work was to figure out the potential mechanism of circ_0010220/miR-503-5p/CDCA4 axis in osteosarcoma progression. Firstly, quantitative RT-qPCR was utilized to measure the expression of circ_0010220 in osteosarcoma cells. Then, osteosarcoma cell proliferation, apoptosis, cell cycle, migration and invasion after loss of circ_0010220 were evaluated using CCK-8, flow cytometry, transwell migration, invasion and tumorigenesis experiments respectively. Circ_0010220 expression was markedly increased in osteosarcoma cells. Additionally, knockdown of circ_0010220 significantly depressed tumor growth. CCK-8 analysis indicated that down-regulation of circ_0010220 inhibited osteosarcoma cells proliferation. Flow cytometry assay showed that knockdown of circ_0010220 induced cell apoptosis and blocked cell cycle in the G1 phase. Meanwhile, cell migration an invasion was reduced by circ_0010220. Furthermore, miR-503-5p was predicted as the target for circ_0010220 and miR-503-5p inhibitors reversed cell growth suppressed through silencing circ_0010220. Then, our study demonstrated that Cell Division Cycle-Associated protein 4 (CDCA4) could be a downstream target of miR-503-5p. Additionally, circ_0010220 down-regulation reduced CDCA4 expression level and the inhibitors of miR-503-5p reversed that. In conclusion, we indicated circ_0010220 can be an important biomarker for osteosarcoma via regulating miR-503-5p and CDCA4.

LINC00265 targets miR-382-5p to regulate SAT1, VAV3 and angiogenesis in osteosarcoma.

We explored the mechanism by which LINC00265 regulates angiogenesis of osteosarcoma cells via the miR-382-5p/spermidine/spermine N1-acetyltransferase-1 (SAT1) and miR-382-5p/vav guanine nucleotide exchange factor 3 (VAV3) axis. Cell scratch assay, Transwell assay and tube formation assay were applied to detect cell migration, invasion and tube formation abilities. The effects of LINC00265 targeting miR-382-5p in osteosarcoma in vivo were studied using a tumour-burden assay. A total of 70 genes potentially involved in osteosarcoma angiogenesis were identified, and a Gene Ontology (GO) analysis found that SAT1 and VAV3 were closely related to angiogenesis. Bioinformatics analysis and clinical experiments confirmed that LINC00265, SAT1 and VAV3 were overexpressed in osteosarcoma and related to a poor prognosis, whereas miR-382-5p was downregulated and associated with a poor prognosis. It was confirmed that LINC00265 promoted the proliferation, migration, invasion and angiogenesis of osteosarcoma cells by targeting miR-382-5p to mediate SAT1 and VAV3. Collectively, LINC00265 might promote proliferation, migration, invasion and angiogenesis by targeting miR-382-5p/SAT1 and miR-382-5p/VAV3 in osteosarcoma.

MiR-135b Induces Osteosarcoma Invasion by the Modulation of FOXO-1 and c-Myc

Background: Osteosarcoma (OS) is the most common type of bone malignancy. Many studies have attempted to find the association between microRNAs and cancer-associated processes. Alterations in miRNA expression through genetic or epigenetic changes, impairment of transcription factors, and ectopic expression of miRNAs induce the development and progression of cancer. Although miR-135b has been thoroughly documented as an oncogene in the majority of studies, some controversies remain about the conflicting role of miR-135b as a tumor-suppressor. Objectives: The present study aimed at investigating the oncogenic and/or tumor-suppressing role of miR-135b in human OS. Methods: In this study, 21 OS tissue samples, along with 21 adjacent bone tissues (normal) as control specimens were collected to analyze the expression of miR-135b. The Saos2 cell-line was transiently transfected with the miR-135b mimic and inhibitor to assess its effect on two critical transcription factors, namely FOXO-1 and c-Myc. qRT-PCR was performed to quantify the expression of miR-135b in both OS tissues and the Saos2 cell-line. The MTT, cell migration, and cell invasion assays were used to characterize the miR-135b function. The western blot analysis was carried out to monitor the targets of miR-135b. Finally, the changes in cellular functions such as migration and invasion, following the transfection of miR-135b mimic and inhibitor, were verified. Results: The results showed that in comparison with the adjacent normal bone tissues, the expression of miR-135b was higher in OS tissue samples, which inversely correlated with the expression rate of FOXO-1, whereas the expression of c-Myc had a direct relationship to miR-135b expression. Functionally, the miR-135b mimic led to an increase in cell proliferation, invasion, and migration of OS cancer cells. Conclusions: MiR-135b induces the proliferation and invasion of OS cells by the degradation of FOXO-1 and upregulation of c-Myc.

Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

Although there are many therapeutic strategies such as surgery and chemotherapy, the prognosis of osteosarcoma (OS) is still far from being satisfactory. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. In the present study, we investigated the anti-OS activity of Alantolactone (ALT), a natural eucalyptone sesquiterpene lactone mainly exists in Inula helenium, and probed the possible mechanism involved. We demonstrated that ALT significantly inhibited cell proliferation of various human OS cell lines while had relative lower cytotoxicity against normal cells. Then, we validated that ALT reduced migration, decreased invasion possibly through reversing epithelial mesenchymal transition (EMT) process and suppressing Matrix metalloproteinases (MMPs). Moreover, we confirmed that ALT promoted apoptosis and arrested cell cycle at G2/M phase of human OS cells in vitro. In addition, we confirmed that ALT restrained tumor growth and metastasis of OS 143 cells in a xenograft model in vivo. Mechanistically, ALT inhibited the activity of Wnt/β-catenin and p38, ERK1/2 and JNK Mitogen Activated Protein Kinases (MAPKs) signal pathway. Notably, the combination of ALT and Wnt/β-catenin inhibitor, as well as the combination of ALT and MAPKs inhibitors resulted in a synergistically effect on inhibiting the proliferation, migration and invasion of OS cells. Collectively, our results validate the ALT may inhibit proliferation, metastasis and promotes apoptosis of human OS cells possibly through suppressing Wnt/β-Catenin and MAPKs signaling pathways.

Pseudogene MSTO2P enhances hypoxia-induced osteosarcoma malignancy by upregulating PD-L1

Hypoxia has been shown to be related to osteosarcoma development and progression. Pseudogene MSTO2P was reported to be dysregulated in hepatocellular carcinoma and lung cancer. However, the mechanism by which MSTO2P-modulated osteosarcoma remains unclear. MSTO2P and PD-L1 expression levels were examined by RT-qPCR and westernblot. Tumor cell invasion was determined by tranwell assay. EMT process was probed by determining E-cadherin and Vimentin levels. Soft agar assay was used to examine anchorage-independent growth of osteosarcoma cells. In vivo tumor growth was measured by xenografting tumor experiment. Hypoxia treatment promoted cell growth, invasion and EMT of osteosarcoma cells. MSTO2P knockdown led to attenuated cell growth, invasion and EMT of osteosarcoma cells under hypoxia condition. More interestingly, our data revealed that MSTO2P was positively associated with tumor growth in immunodeficient mice and human clinical tissues. PD-L1 was shown to act as a key effector for MSTO2P-regulated osteosarcoma progression under hypoxia condition. In conclusion, we unravel a novel mechanism for explaining MSTO2P-involved osteosarcoma progression under hypoxia condition, which will facilitate development of potential diagnostic and therapeutical strategies for osteosarcoma.

Down-regulation of PDGFRβ suppresses invasion and migration in osteosarcoma cells by influencing epithelial-mesenchymal transition.

Osteosarcoma (OS) is the most common malignant bone tumor primarily influencing children and adults. Approximately one-fifth of patients have micrometastasis in the lungs when OS is diagnosed. Platelet-derived growth factor receptor (PDGFR) beta (PDGFRβ) is a subtype of PDGFR. PDGFRβ has been noted to be highly expressed in OS cell lines and patient specimens, and is associated with metastasis and poor prognosis of OS. However, mechanistic insights into the exact role of PDGFRβ in OS pathogenesis and development are still lacking. Here we assessed the effects of PDGFRβ on invasive and migratory abilities, such as the epithelial-mesenchymal transition and phosphatidylinositol 3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR) pathways in HOS cells. Depleting PDGFRβ resulted in reduced migration of HOS cells in the small interfering RNA duplexes specific for the PDGFRβ group compared with the mock and scramble-treated groups in Transwell invasion assays. Using wound-healing assays, we demonstrate the rate of wound healing in the PDGF-BB-stimulated group was higher compared with the mock-treated group. Western blot showed that down-regulation of PDGFRβ decreased the expression of stromal phenotype markers and phosphorylation pathway proteins (PI3K, AKT and mTOR), but the epithelial phenotype marker was increased in HOS cells. Treating HOS cells with PDGF-BB revealed a treatment time-dependent increase of phosphorylated, but not total, PI3K, AKT and mTOR. Taken together, we suggest that PDGFRβ plays an important role in OS invasion, migration and epithelial-mesenchymal transition by influencing the PI3K, Akt and mTOR pathways, hence highlighting PDGFRβ as a potential therapeutic target for OS.

LncRNA‑zinc finger protein 281 downregulates rho‑associated coiled‑coil containing protein kinase 1 by upregulating miR‑144 in osteosarcoma

Zinc finger protein 281 (ZNF281) has been characterized as a tumor suppressive lncRNA in glioma. The present study aimed to analyze the functionality of ZNF281 in osteosarcoma (OS). It was demonstrated that ZNF281 was downregulated in OS tissue specimens and predicted the survival of patients with OS. In tissues from patients with OS, ZNF281 was negatively associated with rho-associated coiled-coil containing protein kinase 1 (ROCK1), but positively associated with miR-144. In the U2OS cell line, ZNF281 overexpression mediated the upregulation of miR-44 and downregulation of ROCK1. miR-144 overexpression led to the downregulation of ROCK1, but failed to affect ZNF281. Expression of ZNF281 and miR-144 resulted in decreased cell migration and invasion, while ROCK1 overexpression resulted in increased invasion and migration of OS cells. In addition, ROCK1 overexpression attenuated the effects of ZNF281 and miR-144 overexpression. Thus, ZNF281 may downregulate ROCK1 by upregulating miR-144 and inhibit cancer cell invasion and migration in OS.

Long non-coding RNA BLACAT1 expedites osteosarcoma cell proliferation, migration and invasion via up-regulating SOX12 through miR-608

BackgroundOsteosarcoma is the most common type of bone malignancy. Increasing evidence indicated that long non-coding RNAs (lncRNAs) possess multiple functions in the development of cancer and can be used as indicators of prognosis and diagnosis. LncRNA BLACAT1 has been found to promote the proliferation of breast cancer cells. However, the role of BLACAT1 in osteosarcoma remains largely unknown. MethodsQRT-PCR analysis was employed to evaluate mRNA expressions. Western blot was performed to measure relevant protein level. Colony formation and EdU assays were conducted to certify proliferative ability. TUNEL assay was finalized to assess apoptotic cells. Wound-healing and transwell assays were utilized for the exploration of migrating and invasive abilities. The subcellular distribution of BLACAT1 was studied by nucleus-cytoplasm separation assay. Relevant mechanical experiments were combined to elucidate molecular relationship between molecules. ResultsBLACAT1 was highly expressed in osteosarcoma. BLACAT1 promoted the proliferation and migration of osteosarcoma cells. BLACAT1 acted as a sponge for miR-608 to augment the expression of Sex determining region Y-box protein 12 (SOX12), the direct target of miR-608. Further, inhibiting miR-608 recovered the repressive effect of silenced BLACAT1 on the malignant behaviors of osteosarcoma cells. ConclusionThis study highlighted the contribution of BLACAT1/miR-608/SOX12 axis to the progression of osteosarcoma, suggesting novel targets for osteosarcoma therapy.

LINC00662 Long Non-Coding RNA Knockdown Attenuates the Proliferation, Migration, and Invasion of Osteosarcoma Cells by Regulating the microRNA-15a-5p/Notch2 Axis.

PurposeOsteosarcoma (OS) is a frequently occurring malignancy in children and adolescents. In this study, we aimed to investigate the effects of the long non-coding RNA (lncRNA) LINC00662 (LINC00662) in OS and the underlying molecular mechanism.MethodsThe expression of LINC00662, microRNA-15a-5p (miR-15a-5p), and Notch2 in OS was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, and invasion of OS cells were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound-healing, and transwell assay. The interactions among LINC00662, miR-15a-5p, and Notch2 were determined by dual-luciferase reporter assays. A tumor xenograft model was established in mice for evaluating tumor growth in vivo.ResultsThe expression of LINC00662 and Notch2 was found to be upregulated in OS, but the expression of miR-15a-5p was downregulated. The results demonstrated that LINC00662 knockdown attenuated the proliferation, migration, and invasion of OS cells and suppressed tumor growth in mice. The study further demonstrated that LINC00662 directly interacted with miR-15a-5p, and that Notch2 was a target of miR-15a-5p. The inhibition of miR-15a-5p or Notch2 overexpression markedly reversed the suppressive effect of sh-LINC00662 on the proliferation, migration, and invasion of OS cells.ConclusionThe study demonstrated that LINC00662 could be a potential biomarker for OS therapy, and LINC00662 knockdown suppressed the proliferation, migration, and invasion of OS cells by regulating the miR-15a-5p/Notch2 axis.

Long-Noncoding RNA PCAT6 Aggravates Osteosarcoma Tumourigenesis via the MiR-143-3p/ZEB1 Axis.

IntroductionThe long-noncoding RNA PCAT6 plays an important regulatory role in the development of several cancers. However, the expression pattern and underlying mechanisms of PCAT6 in osteosarcoma (OS) are yet unknown.MethodsWe used real-time PCR to measure PCAT6 expression in 106 tumor pairs and corresponding non-tumor tissues from OS patients. Statistical analyses were applied to evaluate the prognostic value and associations of PCAT6 expression with clinical parameters. Furthermore, the PCAT6 was silenced with siRNA in OS cells. Moreover, phenotype of PCAT6 silenced OS cells was measured using colony formation, CCK-8, cell migration and invasion assay. Finally, the molecular mechanism of PCAT6/miR-143-3p/ZEB1 axis in OS progression was explored.ResultsThe expression level of PCAT6 in OS tissues was significantly elevated as compared with that in the adjacent normal bone tissues and that high PCAT6 expression closely correlated with the malignant phenotype and poor survival among patients with OS. Multivariate analyses revealed PCAT6 overexpression as an independent prognostic factor for the poor outcome of patients with OS. Functional assay results demonstrated that the knockdown of PCAT6 expression notably suppressed the proliferation, migration, and invasion of OS cells. An elevated PCAT6 level aggravated the malignant phenotype of OS cells via ZEB1 expression upregulation. Mechanistic studies revealed that PCAT6 could sponge endogenous miR-143-3p and inhibit its activity, resulting in an increase in ZEB1 level. Finally, we demonstrated that the tumour-promoting role of PCAT6 in OS was dependent on the regulation of the miR-143-3p/ZEB1 axis.ConclusionThese findings highlight the potential role of PCAT6, which could serve as a valuable prognostic indicator for patients with OS.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

The article "Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis, by B.-G. Tian, Z. Hua, Z.-J. Wang, J. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1030-1040-DOI: 10.26355/eurrev_202002_20153-PMID: 32096182" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20153.

Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis.

BackgroundMetastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches.Materials and MethodsRNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes.ResultsA total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug–gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis.ConclusionWe identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.