Association between PTEN and clinical-pathological features of osteosarcoma

Zhou, Jian; Xiao, Xia; Wang, Wanchun; Luo, Yuan

doi:10.1042/bsr20190954

Cited by 15 publications

(6 citation statements)

References 21 publications

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“…Consequently, PTEN may act as a crucial regulator in OS progression. It was reported that PTEN expression was negatively associated with OS metastasis and survival ( 28 ). Besides, Blüml S showed that PTEN (-/-) displayed increased osteoclast number and bone resorption, indicating the negative regulation of osteoclastogenesis and function by PTEN ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

et al. 2021

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Osteosarcoma (OS) is the most common primary bone cancer characterized by an aggressive phenotype with bone destruction. The prognosis of OS patients remains unoptimistic with the current treatment strategy. Recently, osteoclasts are believed to play a crucial role in cancer bone metastasis. Thus, osteoclast could be a target both in bone destruction and cancer progression in OS. However, mechanisms governing osteoclastogenesis in OS remain poorly understood. miRNA delivered by small extracellular vesicles (sEVs) could mediate cellular communications. In this study, we investigated the effects of sEVs on osteoclastogenesis and osteoclast function, also clarified the underlying mechanism. We herein found that sEVs promoted pre-osteoclast migration, osteoclastogenesis and resorption by exposing RAW264.7 cells to sEVs derived from OS cells. Bioinformatics analysis showed that phosphatase tension homologue (PTEN), and miR-19a-3p were involved in OS progression. Overexpression of miR-19a-3p or sEVs’ miR-19a-3p promoted osteoclast formation and function through PTEN/PI3K/AKT signaling pathway, while inhibition of miR-19a-3p showed the contrary results. The bone marrow macrophages (BMMs) were used to verify the results. OS mice, which were established by subcutaneous injection of OS cells, exhibited increased levels of sEVs’ miR-19a-3p in blood. Moreover, micro-computed tomography (CT) and histomorphometry analysis demonstrated that OS mice exhibited osteopenia with increased number of osteoclasts. In conclusion, miR-19a-3p delivery via OS cell-derived sEVs promotes osteoclast differentiation and bone destruction through PTEN/phosphatidylinositol 3 -kinase (PI3K)/protein kinase B (AKT) signaling pathway. These findings highlight sEVs packaging of miR-19a-3p as a potential target for prevention and treatment of bone destruction and cancer progression in OS patients. And this finding provides a novel potentially therapeutic target for the bone metastasis.

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Section: Discussionmentioning

confidence: 99%

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

et al. 2021

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“…Its loss or deactivation has been reported in the development of osteosarcoma. 35,36 Many noncoding RNAs have been identified, which can bind to PTEN, such as circ-ORC2 and miR-19a 37 and miR-29. 38 An increasing number of studies have shown that PTEN/ PI3K/Akt pathway is involved in the tumorigenesis of osteosarcoma as the loss of function of PTEN may prevent the phosphorylation of PIP2 and decrease the PIP3 and eventually activate the PI3K-Akt pathway to inhibit cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Non-Coding RNA 691 Regulated PTEN/PI3K/AKT Signaling Pathway in Osteosarcoma Through miRNA-9-5p</p>

Yao¹,

Ni²,

Liu³

2020

OTT

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Background: Large amounts of researches indicate that non-coding RNAs play a crucial role in many malignancies. However, the potential mechanisms of non-coding RNAs involved in osteosarcoma tumorigenesis remain elusive. Materials and Methods: The expression of long non-protein coding RNA 691 (lncRNA 691) in cell lines and paired osteosarcoma tissues was compared by qRT-PCR assay. Then, we explored the tumor suppressor function of lncRNA 691 with MTS and colony formation assay. Flow cytometry results showed lncRNA 691 can enhance cell apoptosis. Then, we predicted and verified the negative regulation relationship with miRNA and the miRNA's target gene. Lastly, we revealed the tumorigenesis function of lncRNA-691/miRNA/target gene axis in osteosarcoma. Results: In our study, we disclosed that lncRNA 691 had low expression levels in osteosarcoma cell lines and tissues. Overexpression of lncRNA 691 could suppress the cell proliferation and induce cell apoptosis in MG-63 cell line. Then, bioinformatics analyses were performed and miR-9-5p was found to negatively regulate the lncRNA 691 expression and promote the osteosarcoma tumorigenesis in vitro. PTEN was predicted as the target gene of miR-9-5p. Luciferase reporter assay and RIP assay demonstrated the regulatory network of lncRNA 691/miR-9-5p/PTEN. We revealed that PTEN was downregulated by the overexpression of miR-9-5p and upregulated by the overexpression of lncRNA 691. At last, the apoptosis-associated protein of the lncRNA 691/miR-9-5p/PTEN/PI3K/AKT was further demonstrated. Conclusion: LncRNA 691/miR-9-5p could regulate the tumorigenesis by regulating the PTEN/PI3K/AKT signal pathway in osteosarcoma.

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“…There are other less frequent alterations, such as FGFR1, which, as demonstrated by Amary et al in 288 patients, occurs in up to 18.5% of patients and is associated with a worse response to chemotherapy and, therefore, a worse prognosis [ 39 ]. On the other hand, there are good prognostic factors, such as PTEN, which was highlighted by Zhou et al in a review of 13 articles that included 580 patients with osteosarcoma; a positive expression of PTEN was associated with a better prognosis, including a lower incidence of metastasis and larger differentiated tumours, which were, therefore, less aggressive [ 40 ]. We have previously noted that there is a difference between osteosarcoma in adults and in children, where the most frequent alterations in both cases are alterations in the expression of the p53 and Rb genes.…”

Section: Genetic Markersmentioning

confidence: 99%

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations

Pekarek

Torre-Escuredo

Fraile-Martínez

et al. 2022

IJMS

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Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.

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Association between PTEN and clinical-pathological features of osteosarcoma

Cited by 15 publications

References 21 publications

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

Osteosarcoma Cell-Derived Small Extracellular Vesicles Enhance Osteoclastogenesis and Bone Resorption Through Transferring MicroRNA-19a-3p

<p>Long Non-Coding RNA 691 Regulated PTEN/PI3K/AKT Signaling Pathway in Osteosarcoma Through miRNA-9-5p</p>

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations

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