mi<scp>RNA</scp> profiling identifies deregulated mi<scp>RNA</scp>s associated with osteosarcoma development and time to metastasis in two large cohorts

Andersen, Gitte Brinch; Knudsen, Alice; Hager, Henrik; Hansen, Lise Lotte; Tost, Jörg

doi:10.1002/1878-0261.12154

Cited by 47 publications

(43 citation statements)

References 64 publications

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“…Herein, in line with previous studies, we showed that the expression of miR-135b is aberrantly upregulated in primary tumors of patients with OS compared with the adjacent normal tissues (14,16,35,36). The change in the expression of miR-135b affects some molecular pathways involved in the onset and progression of neoplasia (4). The proliferation, invasion, and metastasis are 3 cellular events that are critical for cancer progression.…”

Section: Discussionsupporting

confidence: 88%

“…Osteosarcoma (OS), known as osteogenic sarcoma, is an aggressive and primary bone tumor with an incidence rate of 4 to 5 cases per million, affecting children and adolescents (1)(2)(3)(4)(5). More importantly, it accounts for 19% of all malignant tumors of bone (6) with a higher prevalence in young males compared with young females (5), and its etiology is still opaque (4,7). It affects the metaphysis of long bones, such as the distal femur, and it seems that rapid bone growth occurring in adolescents is related to the promotion of malignancy (8).…”

Section: Introductionmentioning

confidence: 99%

“…MiRNAs mainly consist of 22 nucleotides involved in RNA silencing by post-transcriptional regulation of gene expression, changing the stability of specific mRNAs, or obstructing the translation of some mR-NAs. Hence, any alteration in the expression of miRNAs may influence the expression of tumor-suppressor and oncogene genes (4,9,(13)(14)(15)(16). Gao et al studied the role of miRNA expression in the development of OS (2).…”

Section: Introductionmentioning

confidence: 99%

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

Tahbazlahafi¹,

Paknejad²,

Shahmohamadnejad³

et al. 2020

Int J Cancer Manag

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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.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Tahbazlahafi¹,

Paknejad²,

Shahmohamadnejad³

et al. 2020

Int J Cancer Manag

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“…About 75% of the patients are 15-25 years old, and most are male. The prognosis of osteosarcoma patients is very poor [ 1 ], and new and more effective methods of treatment of this disease are greatly needed.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-506-3p inhibits osteosarcoma cell proliferation and metastasis by suppressing RAB3D expression

Wang

Qiu

Zhenjun

et al. 2018

Aging

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Osteosarcoma is an aggressive bone tumor primarily affecting children and adolescents. Its cause is not yet fully understood, and there is an urgent need for more effective treatment. In the present study we identified several miRNAs whose expression is altered in osteosarcoma compared to adjacent normal tissue. Moreover, expression levels of one of those miRNAs, miR-506-3p, correlated negatively with expression of RAB3D (a Ras-related protein). Suppression of miR-506-3p in osteosarcoma led to increased expression of RAB3D, which in turn led to increased CDK4 (cyclin-dependent kinase 4) and MMP9 (matrix metalloprotein 9) activities. Our results suggest that miR-506-3p acts as a tumor suppressor in osteosarcoma and that its downregulation leads to tumor cell proliferation and metastasis due to upregulation of RAB3D- and CDK4-mediated signaling. miR-506-3p thus appears be a potentially useful target for adjuvant therapy in osteosarcoma patients.

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“…Small RNAs have the potential to become prognostic biomarkers of OS (listed in Table 4) [100][101][102]. An example of this kind of RNA deregulated in osteosarcoma is miR-421 [94].…”

Section: Small Rnas In Osteosarcomamentioning

confidence: 99%

Molecular Biology of Osteosarcoma

Czarnecka

Synoradzki

Firlej

et al. 2020

Cancers

213

186

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Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond–Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK–ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.

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miRNA profiling identifies deregulated miRNAs associated with osteosarcoma development and time to metastasis in two large cohorts

Cited by 47 publications

References 64 publications

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

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

MicroRNA-506-3p inhibits osteosarcoma cell proliferation and metastasis by suppressing RAB3D expression

Molecular Biology of Osteosarcoma

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