Identification of Prognostic and Predictive Osteosarcoma Biomarkers

Zamborský, Radoslav; Kokavec, M; Harsanyi, Stefan; Danišovič, Ľuboš

doi:10.3390/medsci7020028

Cited by 37 publications

(45 citation statements)

References 90 publications

(88 reference statements)

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“…4,5 Although more and more tumor-related regulators have been identified, almost no commonly-accepted markers have been established for the clinical application. [6][7][8] Thus, it is urgent to make clear the key molecule involved in the growth and metastasis of OS for the improvement of early detection and targeted treatment of OS.…”

Section: Introductionmentioning

confidence: 99%

<p>SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708</p>

Sun

et al. 2020

CMAR

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Background: Growing studies have suggested the dysregulation of long non-coding RNAs (lncRNAs) in several tumors, including osteosarcoma (OS). However, limited studies report metastasis-associated lncRNAs in OS. Our present study aimed to explore the roles of lncRNA LINC00514 (LINC00514) in OS. Materials and Methods: The LINC00514 expression was measured using qPCR assays in OS tissues and cell lines. The clinical significance of LINC00514 expression in OS patients was analyzed using chi-square test, Kaplan-Meier assays and multivariate analysis. The possible effects of LINC00514 in tumor cellular progression were determined using a series of functional assays. The mechanisms of LINC00514 action were explored through bioinformatics, luciferase reporter assays and RT-PCR assays. The mechanisms involved the upregulation of LINC00514 expression in OS were determined using luciferase reporter and chromatin immunoprecipitation (ChIP) assays. Results: We showed that LINC00514 expressions were distinctly upregulated in both OS tissues and cell lines, especially in advanced cases. High levels of LINC0051 were positively correlated with advanced tumor stages, distant metastasis, and reduced survival of patients with OS. Functional experiments indicated that silencing of LINC00514 suppressed the ability of cell growth, colony formation and metastasis, whereas promoted cell apoptosis in vitro. Mechanistic investigation revealed that LINC00514 could directly bind to miR-708 and effectively serve as a ceRNA for miR-708. In addition, LINC00514 was upregulated by the transcription factor SP1. Conclusion: Our findings revealed SP1-induced upregulation of LINC00514 as an oncogene in OS through competitively binding to miR-708, suggesting that there are potential diagnostic and treatment values of LINC00514 in OS.

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Section: Introductionmentioning

confidence: 99%

<p>SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708</p>

Sun

et al. 2020

CMAR

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“…Studies have revealed that MMPs such as MMP-2, MMP-3, and MMP-9 are involved in osteosarcoma progression and metastasis [ 19 , 53 , 54 ]. Interestingly, high MMP-9 expression is associated with poor prognosis in patients with osteosarcoma in several meta-analysis reports [ 55 – 57 ]. This evidence is in accordance with our finding in clinical specimens in osteosarcoma.…”

Section: Discussionmentioning

confidence: 99%

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

Liu

Chen

Chang³

et al. 2020

J Exp Clin Cancer Res

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Background Osteosarcoma is generally reported among younger individuals and has a very poor prognosis, particularly for the development of metastasis. However, more effective metastatic biomarkers and therapeutic methods are absent. Monocyte chemoattractant protein-1 (MCP-1) is involved in cancer progression and inflammatory recruitment. Although previous studies have reported higher serum MCP-1 levels in patients with osteosarcoma, the role of MCP-1 in osteosarcoma progression remains to be addressed. Methods The osteosarcoma cell migratory ability was assessed by transwell migration assay. The MCP-1 and MMP-9 expression levels were analyzed by Western blot and qPCR. The signal activation was conducted by Western blot. The in vivo mouse experiment and tumor tissue array were performed to confirm our findings in vitro. Results The present study demonstrates that MCP-1 regulates cell mobility through matrix metalloproteinase (MMP)-9 expression in osteosarcoma cells. Moreover, MCP-1 promotes MMP-9 expression, cell migration, and cell invasion by mediating CCR2, c-Raf, MAPK, and AP-1 signal transduction. Using MCP-1 knockdown stable cell lines, we found that MCP-1 knockdown reduces MMP-9 expression and cell mobility. Finally, we found high MCP-1 expression levels in osteosarcoma specimens. Conclusions Our results provide prognostic value of MCP-1 in osteosarcoma by promoting MMP-9 expression.

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“…Prognostic and predictive biomarkers refer to biological characteristics that give information on the possible course of cancer and the patient's overall outcome irrespective of the therapy and predict the potential therapeutic outcome of a targeted treatment. The CRISPR/Cas platform can serve as a valuable tool to identify these biomarkers though assessing genetic or epigenetic changes within the tumor tissue (45,46).…”

Section: Prognostic and Predictive Biomarkers Identification Via Crismentioning

confidence: 99%

CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer

et al. 2020

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The clustered regularly interspaced short palindromic repeats system has demonstrated considerable advantages over other nuclease-based genome editing tools due to its high accuracy, efficiency, and strong specificity. Given that cancer is caused by an excessive accumulation of mutations that lead to the activation of oncogenes and inactivation of tumor suppressor genes, the CRISPR/Cas9 system is a therapy of choice for tumor genome editing and treatment. In defining its superior use, we have reviewed the novel applications of the CRISPR genome editing tool in discovering, sorting, and prioritizing targets for subsequent interventions, and passing different hurdles of cancer treatment such as epigenetic alterations and drug resistance. Moreover, we have reviewed the breakthroughs precipitated by the CRISPR system in the field of cancer immunotherapy, such as identification of immune system-tumor interplay, production of universal Chimeric Antigen Receptor T cells, inhibition of immune checkpoint inhibitors, and Oncolytic Virotherapy. The existing challenges and limitations, as well as the prospects of CRISPR based systems, are also discussed.

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Identification of Prognostic and Predictive Osteosarcoma Biomarkers

Cited by 37 publications

References 90 publications

<p>SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708</p>

<p>SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708</p>

Monocyte Chemoattractant Protein-1 promotes cancer cell migration via c-Raf/MAPK/AP-1 pathway and MMP-9 production in osteosarcoma

CRISPR/Cas: From Tumor Gene Editing to T Cell-Based Immunotherapy of Cancer

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