Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is needed to explore novel biological markers for early diagnosis and treatment of human osteosarcoma. Sphingosine kinase 2 (SphK2) expression and potential functions in osteosarcoma were studied. We demonstrate that SphK2 is over-expressed in multiple human osteosarcoma tissues and established human osteosarcoma cell lines. Silence of SphK2 by targeted-shRNAs inhibited osteosarcoma cell growth, and induced cell apoptosis. On the other hand, exogenous over-expression of SphK2 could further promote osteosarcoma cell growth. Notably, microRNA-19a-3p ("miR-19a-3p") targets the 3' UTR (untranslated region) of SphK2 mRNA. Remarkably, forced-expression of miR-19a-3p silenced SphK2 and inhibited osteosarcoma cell growth. In vivo, SphK2 silence, by targeted-shRNA or miR-19a-3p, inhibited U2OS tumor growth in nude mice. These results suggest that SphK2 could be a novel and key oncotarget protein for OS cell progression.
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PMID:SphK2 over-expression promotes osteosarcoma cell growth. 2928 69

Osteosarcoma is recognized as a malignant tumor in the skeletal system. Long non-coding RNAs (lncRNAs) have been exhibited to play crucial roles in osteosarcoma development. Our current study focused on the biological effects and mechanism of LINC00968 in osteosarcoma pathogenesis. We observed that LINC00968 was dramatically elevated in osteosarcoma cells including U2OS, MG63, Saos-2, SW1353, and 143-B cells compared to human osteoblast cell line hFOB. Silence of LINC00968 inhibited osteosarcoma cell growth and proliferation in vitro. Reversely, overexpression of LINC00968 promoted osteosarcoma cell survival and cell colony formation ability in Saos-2 and 143-B cells. In addition, LINC00968 was able to induce osteosarcoma cell migration and invasion through up-regulating MMP-2 and MMP-9 protein levels. The phosphoinosmde-3-kinase/Protein Kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway has been reported to participate in several cancer types. Here, in our study, we found that PI3K/AKT/mTOR pathway was involved in osteosarcoma progression. Knockdown of LINC00968 inactivated PI3K/AKT/mTOR signaling pathway in vitro. Subsequently, in vivo tumor xenografts were established using 143-B cells to investigate whether LINC00968 can induce osteosarcoma development in vivo. Consistently, it was indicated that inhibition of LINC00968 significantly inhibited osteosarcoma progression in vivo. Taken these together, in our research, LINC00968 could be provided as a novel prognostic biomarker and therapeutic target in osteosarcoma diagnosis and treatment.
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PMID:LINC00968 functions as an oncogene in osteosarcoma by activating the PI3K/AKT/mTOR signaling. 2990 19

Osteosarcoma (OS) is one of the most common primary bone tumors in children and young adults. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Thus, it is important to explore novel effective therapeutic targets in the treatment of osteosarcoma. Diacylglycerol kinase zeta (DGKZ) is a recently identified gene potentially associated with certain human carcinogenesis. However, the role of DGKZ in proliferation of osteosarcoma is still unclear. In this study, DGKZ's expression was firstly investigated in OS tumor samples and correlated with poor outcome in OS patients. Silence of DGKZ by shRNA hampered osteosarcoma cell growth and promoted cell apoptosis in vitro. In vivo, DGKZ's knockout also suppressed xenograft tumor proliferation as determined by bioluminescence imaging and weight/volume measurements. Meanwhile, Affymetrix GeneChip and Ingenuity Pathway Analysis (IPA) revealed that DGKZ knockdown resulted in a decreased activity of MYC pathway, and several target genes expression in MYC pathway were altered, including CCND1, CDKN2B, CDK6, PCNA, and EGR1. Furthermore, immunoprecipitation coupled with mass spectrometry (IP-MS) analysis was used to identify proteins that interacted with DGKZ in OS cells and revealed ERK1/2, a key MYC-interactor, to associate with DGKZ. Together, our study demonstrated that DGKZ might act as an oncogene in osteosarcoma via its possible interaction with ERK1/2 and MYC pathway.
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PMID:DGKZ Acts as a Potential Oncogene in Osteosarcoma Proliferation Through Its Possible Interaction With ERK1/2 and MYC Pathway. 3066 72

The pulmonary metastasis of osteosarcoma (OS) occurs commonly, which resulted from anoikis resistant (AR) of tumor cells as reported by previous studies, but the exact roles of AR in osteosarcoma were not fully studied. Our previous investigations showed fatty acid synthase (FASN) was relating to clinical features of patients with OS. In this study, we aim to explore the functions of FASN in the AR OS cells in vitro and in vivo and study the downstream effectors of FASN. In the present study, we used our established cell model to study the AR. We revealed that AR promoted cell proliferation and migration as determined by colony formation assay and transwell assay. In addition, AR assisted tumor growth in vivo. In the AR cells, the expression of FASN was higher. Thus, we constructed lentiviruses to silence or overexpress FASN in four cell lines to study functions of FASN. Silence of FASN reduced cell colonies and migration while overexpression of FASN increased colonies and migration in suspended cells. Loss of functions of FASN induced cell apoptosis in suspended OS cells while gain of function of FASN suppressed apoptosis as determined by flow cytometry. We found the levels of p-ERK1/2 and Bcl-xL declined when FASN was silenced while they increased when FASN was overexpressed. In addition, results showed that the levels of FASN and its potential related molecules (p-ERK1/2 and Bcl-xL) increased in 143B-AR and MG-63-AR cells. In vivo study showed that inhibition of FASN decreased pulmonary metastasis of OS. In conclusion, we showed that anoikis resistant and FASN as two interactional factors facilitated the progress of osteosarcoma.
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PMID:Anoikis resistant mediated by FASN promoted growth and metastasis of osteosarcoma. 3093 32