Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature

Kebudi, Rejin; Özger, Harzem; Kizilocak, Hande; Bay, Sema Büyükkapu; Bılgıç, Bilge

doi:10.1002/pbc.26067

Cited by 21 publications

(15 citation statements)

References 21 publications

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“…With the promotion of radical surgery and high-dose chemotherapy, the 5-year survival rate of patients with osteosarcoma has increased to approximately 70% (11). However, there a considerable number of patients with this disease still suffer from tumor recurrence and distant metastasis following complex treatment (12). Distant metastasis is one of the most important reasons for the failure of treatment in the majority of patients with osteosarcoma (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Liu

et al. 2018

Int J Oncol

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Osteosarcoma has become one of the most common primary malignant tumors affecting children and adolescents. Although increasing evidence has indicated that microRNAs (miRNAs or miRs) play important roles in the development of osteosarcoma, the expression of miR‑27a‑3p and its effects on osteosarcoma are not yet fully understood. In the present study, our data demonstrated that the expression of miR‑27a‑3p in osteosarcoma cell lines was significantly higher than that in the normal human osteoblastic cell line, hFOB 1.19 cell (P<0.01). In order to explore the role of miR‑27a‑3p in the development and progression of osteosarcoma, the expression of miR‑27a‑3p was inhibited by transfection of the MG-63 cells with miR‑27a‑3p inhibitor. The results revealed that the cell proliferative ability significantly decreased (P<0.01), the number of apoptotic cells significantly increased (P<0.01) and the number of cells passing through the Transwell membrane was significantly reduced in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). At the same time, the expression of E-cadherin and α-catenin was significantly upregulated (P<0.01), while the expression of vimentin was significantly downregulated in the group transfected with the miR‑27a‑3p inhibitor (P<0.01). Our results also revealed that the mRNA expression of ten-eleven translocation 1 (TET1) in the osteosarcoma cells was significantly downregulated compared with that in the hFOB 1.19 cells (P<0.01). Luciferase reporter system analysis indicated that miR‑27a‑3p recognized the TET1 3'-UTR. The protein expression of TET1 significantly increased in the group transfected with the miR‑27a‑3p inhibitor. The results from CCK-8 assay, flow cytometric assay and Transwell invasion analysis revealed that TET1 knockdown inhibited the biological effects induced by the downregulation of miR‑27a‑3p. Taken together, the findings of this study indicate that miR‑27a‑3p is upregulated, while TET1 is downregulated in human osteosarcoma cells. miR‑27a‑3p inhibition suppresses the proliferation and invasion of osteosarcoma cells, and promotes cell apoptosis via the negative regulation of TET1. miR‑27a‑3p/TET1 may thus be a potential target for the treatment of osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Liu

et al. 2018

Int J Oncol

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“…An important consideration in these patients is the possibility of genetic predisposition, as the constellation of hematologic malignancy and sarcoma is suspicious for germline p53 mutations . However, family history is rarely reported in many studies …”

Section: Benign and Malignant Bone Tumorsmentioning

confidence: 99%

“…Instead, regular follow‐up with a thorough history and physical exam is recommended . It is important that patients have long‐term follow‐up to monitor for clinical signs of malignant degeneration such as rapid enlargement (especially after skeletal maturity), as radiation‐induced sarcomas are known to develop more than 15 years after HSCT …”

Section: Benign and Malignant Bone Tumorsmentioning

confidence: 99%

Musculoskeletal complications following total body irradiation in hematopoietic stem cell transplant patients

Jackson

Mostoufi‐Moab

Hill‐Kayser

et al. 2017

Pediatric Blood & Cancer

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Total body irradiation (TBI) is commonly used in conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) to treat benign and malignant disease. Though life-saving, these therapies place patients at risk for important side effects, including musculoskeletal complications such as short stature, osteonecrosis, slipped capital femoral epiphysis, and the development of benign and malignant bone tumors. With an increasing number of HSCT survivors, there is a growing need for awareness of the musculoskeletal complications of HSCT and TBI.

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“…However, due to a high degree of metastasis and recurrence, the outcome of patients with osteosarcoma remains unsatisfactory (2). Although the molecular mechanisms of osteosarcoma have attracted widespread attention, those involved in disease progression have not been fully elucidated (3). Therefore, investigating the molecular mechanism underlying the development of osteosarcoma may aid the identification of novel biomarkers and potential targets for the diagnosis and treatment of the disease (4).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‑145‑5p inhibits osteosarcoma cell�proliferation by targeting E2F transcription factor 3

Li¹,

Pan²,

Lu³

et al. 2020

Int J Mol Med

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Osteosarcoma is a common type of bone tumor that primarily occurs in children and young adults. MicroRNA (miRNA/miR) dysregulation is associated with the progression of osteosarcoma; therefore, the aim of the present study was to investigate the biological functions and molecular mechanisms of miR-145-5p in osteosarcoma. The expression of miR-145-5p in osteosarcoma tissues and cell lines was quantified using reverse transcription-quantitative PCR (RT-qPCR). The effect of miR-145-5p on the proliferation of osteosarcoma cells was detected using cell counting Kit-8 and colony formation assays, as well as cell cycle distribution analysis. The effect of miR-145-5p on tumor growth was further investigated in vivo using a subcutaneous tumor model in nude mice. The interaction between miR-145-5p and E2F transcription factor 3 (E2F3) was determined using bioinformatics analysis, a luciferase assay, RT-qPCR and western blotting. The results revealed that miR-145-5p expression was decreased in osteosarcoma cell lines and tissues compared with the corresponding normal controls. Increased miR-145-5p expression inhibited the proliferation and colony formation ability of osteosarcoma cells, and induced G 1 phase arrest. Furthermore, mice injected with tumor cells overexpressing miR-145-5p exhibited smaller tumors than those in the control group. Further investigation revealed that miR-145-5p binds to and decreases the expression of E2F3. In addition, the mRNA levels of E2F3 were negatively associated with miR-145-5p in osteosarcoma tissues, and increasing E2F3 expression abrogated the inhibitory effects of miR-145-5p on osteosarcoma cells. collectively, the results obtained in the present study suggest that miR-145-5p may suppress the progression of osteosarcoma, and may serve as a useful biomarker for the diagnosis of osteosarcoma, as well as a therapeutic target.

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Osteosarcoma After Hematopoietic Stem Cell Transplantation in Children and Adolescents: Case Report and Review of the Literature

Cited by 21 publications

References 21 publications

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

miR-27a-3p promotes the malignant phenotypes of osteosarcoma by targeting ten-eleven translocation 1

Musculoskeletal complications following total body irradiation in hematopoietic stem cell transplant patients

MicroRNA‑145‑5p inhibits osteosarcoma cell�proliferation by targeting E2F transcription factor 3

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