Publications by authors named "Emel Rothzerg"

6 Publications

  • Page 1 of 1

Upregulation of 15 Antisense Long Non-Coding RNAs in Osteosarcoma.

Genes (Basel) 2021 Jul 26;12(8). Epub 2021 Jul 26.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA 6009, Australia.

The human genome encodes thousands of natural antisense long noncoding RNAs (lncRNAs); they play the essential role in regulation of gene expression at multiple levels, including replication, transcription and translation. Dysregulation of antisense lncRNAs plays indispensable roles in numerous biological progress, such as tumour progression, metastasis and resistance to therapeutic agents. To date, there have been several studies analysing antisense lncRNAs expression profiles in cancer, but not enough to highlight the complexity of the disease. In this study, we investigated the expression patterns of antisense lncRNAs from osteosarcoma and healthy bone samples (24 tumour-16 bone samples) using RNA sequencing. We identified 15 antisense lncRNAs (, , , , , , , , , , , , , and ) that were upregulated in tumour samples compared to bone sample controls. Further, we performed real-time polymerase chain reaction (RT-qPCR) to validate the expressions of the antisense lncRNAs in 8 different osteosarcoma cell lines (SaOS-2, G-292, HOS, U2-OS, 143B, SJSA-1, MG-63, and MNNG/HOS) compared to hFOB (human osteoblast cell line). These differentially expressed IncRNAs can be considered biomarkers and potential therapeutic targets for osteosarcoma.
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http://dx.doi.org/10.3390/genes12081132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394133PMC
July 2021

Current research progress in targeted anti-angiogenesis therapy for osteosarcoma.

Cell Prolif 2021 Sep 26;54(9):e13102. Epub 2021 Jul 26.

Division of Regenerative Biology, School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Osteosarcoma (OS) is the most common primary malignant bone tumour with a peak in incidence during adolescence. Delayed patient presentation and diagnosis is common with approximately 15% of OS patients presenting with metastatic disease at initial diagnosis. With the introduction of neoadjuvant chemotherapy in the 1970s, disease prognosis improved from 17% to 60%-70% 5-year survival, but outcomes have not significantly improved since then. Novel and innovative therapeutic strategies are urgently needed as an adjunct to conventional treatment modalities to improve outcomes for OS patients. Angiogenesis is crucial for tumour growth, metastasis and invasion, and its prevention will ultimately inhibit tumour growth and metastasis. Dysregulation of angiogenesis in bone microenvironment involving osteoblasts and osteoclasts might contribute to OS development. This review summarizes existing knowledge regarding pre-clinical and developmental research of targeted anti-angiogenic therapy for OS with the aim of highlighting the limitations associated with this application. Targeted anti-angiogenic therapies include monoclonal antibody to VEGF (bevacizumab), tyrosine kinase inhibitors (Sorafenib, Apatinib, Pazopanib and Regorafenib) and human recombinant endostatin (Endostar). However, considering the safety and efficacy of these targeted anti-angiogenesis therapies in clinical trials cannot be guaranteed at this point, further research is needed to completely understand and characterize targeted anti-angiogenesis therapy in OS.
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http://dx.doi.org/10.1111/cpr.13102DOI Listing
September 2021

12 Survival-related differentially expressed genes based on the TARGET-osteosarcoma database.

Exp Biol Med (Maywood) 2021 Apr 29:15353702211007410. Epub 2021 Apr 29.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA 6009, Australia.

The Therapeutically Applicable Research to Generate Effective Treatments (TARGET) project aims to determine molecular changes that drive childhood cancers, including osteosarcoma. The main purpose of the program is to use the open-source database to develop novel, effective, and less toxic therapies. We downloaded TARGET-OS RNA-Sequencing data through R studio and merged the mRNA expression of genes with clinical information (vital status, survival time and gender). Further, we analyzed differential gene expressions between dead and alive patients based on TARGET-OS project. By this study, we found 5758 differentially expressed genes between deceased and alive patients with a false discovery rate below 0.05; 4469 genes were upregulated in deceased patients compared to alive, whereas 1289 genes were downregulated. The survival-related genes were obtained using Kaplan-Meier survival analysis and Cox univariate regression (KM < 0.05 and Cox -value < 0.05). Out of 5758 differentially expressed genes, only 217 have been associated with overall survival. Eight survival-related downregulated genes (, , , , , , , and ) and four survival-related upregulated genes (, , and ) were selected for further analysis as potential independent prognostic candidate genes. This study may help to discover novel prognostic markers and potential therapeutic targets for osteosarcoma.
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http://dx.doi.org/10.1177/15353702211007410DOI Listing
April 2021

Alternative splicing of leptin receptor overlapping transcript in osteosarcoma.

Exp Biol Med (Maywood) 2020 10 12;245(16):1437-1443. Epub 2020 Aug 12.

Perron Institute for Neurological and Translational Science, QEII Medical Centre, Nedlands, WA 6009, Australia.

Impact Statement: Osteosarcoma (OS, also known as osteogenic sarcoma) is the most common primary malignancy of bone in children and adolescents. The molecular mechanisms of OS are extremely complicated and its molecular mediators remain to be elucidated. We sequenced total RNA from 18 OS bone samples (paired normal-tumor biopsies). We found statistically significant (FDR <0.05) 26 differentially expressed transcript variants of gene with different expressions in normal and tumor samples. These findings contribute to the understanding of molecular mechanisms of OS development and provide encouragement to pursue further research.
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http://dx.doi.org/10.1177/1535370220949139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553092PMC
October 2020

The Hippo in the room: Targeting the Hippo signalling pathway for osteosarcoma therapies.

J Cell Physiol 2021 03 22;236(3):1606-1615. Epub 2020 Jul 22.

School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia.

Osteosarcoma (OS) is a primary malignant bone tumour which usually occurs in children and adolescents. OS is primarily a result of chromosomal aberrations, a combination of acquired genetic changes and, hereditary, resulting in the dysregulation of cellular functions. The Hippo signalling pathway regulates cell and tissue growth by modulating cell proliferation, differentiation, and migration in developing organs. Mammalian STE20-like 1/2 (MST1/2) protein kinases are activated by neurofibromatosis type 2, Ras association domain family member 2, kidney and brain protein, or other factors. Interactions between MST1/2 and salvador family WW domain-containing protein 1 activate large tumour suppressor kinase 1/2 proteins, which in turn phosphorylate the downstream Yes-associated protein 1/transcriptional coactivator with PDZ-binding motif (YAP/TAZ). Moreover, dysregulation of this pathway can lead to aberrant cell growth, resulting in tumorigenesis. Interestingly, small molecules targeting the Hippo signalling pathways, through affecting YAP/TAZ cellular localisation and their interaction with members of the TEA/ATTS domain family of transcriptional enhancers are being developed and hold promise for the treatment of OS. This review discusses the existing knowledge about the involvement of the Hippo signalling cascade in OS and highlights several small molecule inhibitors as potential novel therapeutics.
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http://dx.doi.org/10.1002/jcp.29967DOI Listing
March 2021

Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers.

Cell Prolif 2020 Feb 22;53(2):e12746. Epub 2019 Dec 22.

Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Human high-temperature requirement protein 1 (HTRA1) is a member of serine proteases and consists of four well-defined domains-an IGFBP domain, a Kazal domain, a protease domain and a PDZ domain. HTRA1 is a secretory protein and also present intracellularly and associated with microtubules. HTRA1 regulates a broad range of physiological processes via its proteolytic activity. This review examines the role of HTRA1 in bone biology, osteoarthritis, intervertebral disc (IVD) degeneration and tumorigenesis. HTRA1 mediates diverse pathological processes via a variety of signalling pathways, such as TGF-β and NF-κB. The expression of HTRA1 is increased in arthritis and IVD degeneration, suggesting that HTRA1 protein is attributed to cartilage degeneration and disease progression. Emerging evidence also suggests that HTRA1 has a role in tumorigenesis. Further understanding the mechanisms by which HTRA1 displays as an extrinsic and intrinsic regulator in a cell type-specific manner will be important for the development of HTRA1 as a therapeutic target.
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http://dx.doi.org/10.1111/cpr.12746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048211PMC
February 2020
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