MicroRNAs and osteosarcoma: Potential targets for inhibiting metastasis and increasing chemosensitivity

Soghli, Negin; Ferns, Gordon A.; Sadeghsoltani, Fatemeh; Qujeq, Durdi; Yousefi, Tooba; Vaghari‐Tabari, Mostafa

doi:10.1016/j.bcp.2022.115094

Cited by 24 publications

(19 citation statements)

References 203 publications

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“… 33 , 34 In OS, PI3K/AKT pathway not only supports the initiation and progression of tumor, but also contributes to the metabolic reprogramming and cellular transformation required for migration and invasion. 38 , 39 In addition, PI3K/AKT pathway can crosstalk with other oncogenic signals such as WNT signaling to dictate cellular changes such as EMT. 40 One of the remaining questions of our study is how DPY30 regulates the activity of PI3K/AKT signaling?…”

Section: Discussionmentioning

confidence: 99%

DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway

Chen

Cao

et al. 2022

Eur J Histochem

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Osteosarcoma (OS) is characterized by aggressive features including invasiveness and high incidence of metastasis. OS patients with metastases are difficult to treat and suffer from a poor prognosis. DPY30 (protein dpy-30 homolog) is a key component of SET1/MLL family of H3K4 methyltransferases, which is implicated in the progression of multiple cancers. However, the potential functional engagement of DPY30 in OS remains to be unveiled. The objective of this study is to investigate the potential roles of DPY30 in the regulation of malignant phenotypes of OS cells. We examined DPY30 expression from a published dataset (GSE28424) as well as in OS tissues and adjacent normal tissues from OS patients. The association of DPY30 expression level and clinicopathologic parameters was assessed by Chi-square test. The role of DPY30 in regulating the malignant phenotype of OS cells and tumorigenesis was examined by in vitro functional assays and xenograft mouse model. We reported an upregulation of DPY30 in OS tumor tissues in both published dataset and clinical samples. A high level of DPY30 expression was associated with larger tumor size and more metastasis in OS patients, as well as poor overall survival. DPY30 knockdown in OS cells significantly impairs proliferation, migration and invasion, but induced cellular apoptosis. We further demonstrated that the agonist of PI3K/AKT pathway can rescue the inhibitory effects of DPY30 knockdown in OS cells. Together, our data indicate that DPY30 functions as an oncogene to promote the malignancy of OS cells possibly through PI3K/AKT pathway. The dependency of OS cells on DPY30 overexpression is a targetable vulnerability in OS cells.

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Section: Discussionmentioning

confidence: 99%

DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway

Chen

Cao

et al. 2022

Eur J Histochem

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“…These molecules can either activate or inhibit various steps of the Wnt signaling pathway. As for tumor pathogenesis and prognosis, miRNAs act as oncogenes and regulate the expression of genes posttranscriptionally, and they are implicated in OS pathogenesis, indicating a more promising application 224 . miR‐429 inhibits OS progression by targeting homologous cassette A9 (HOXA9, HOX gene), thereby suppressing tumor cells proliferation, migration, and invasion and attenuating the Wnt/β‐catenin protein signaling pathway 225 .…”

Section: Mechanism Of Targeting Signaling Pathwaysmentioning

confidence: 99%

“…As for tumor pathogenesis and prognosis, miRNAs act as oncogenes and regulate the expression of genes posttranscriptionally, and they are implicated in OS pathogenesis, indicating a more promising application. 224 miR-429 inhibits OS progression by targeting homologous cassette A9 (HOXA9, HOX gene), thereby suppressing tumor cells proliferation, migration, and invasion and attenuating the Wnt/β-catenin protein signaling pathway. 225 Yang et al 226 reported that miR-183 targets low-density lipoprotein receptor-related protein 6 (LRP6), which regulates the Wnt/β-connexin signaling pathway and is a downstream effector of LRP6.…”

Section: 12mentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb‐preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β‐catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD‐1/PD‐L1, MAPK, and NF‐κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway‐based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

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“…It has been identified that the presence of miRNAs has a vital role in the life cycle of organisms and dysregulation in their expression has caused the occurrence of various disorders. Today, the relationship between different diseases such as different cancers [114,115], diabetes [116,117], obesity [118,119], liver fibrosis [120], osteosarcoma [121], disorders related to the nervous system [83], etc., have been reported with aberrant expression of miRNAs [122], and this field is of great interest to many researchers. In this day and age, the number of researchers working in this field is increasing day by day.…”

Section: Concluding Remarks and Future Viewsmentioning

confidence: 99%

MicroRNAs; their therapeutic and biomarker properties

Dargahlou

Pouresmaeil

Goh

2023

Cell. Mol. Biomed. Rep.

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MicroRNAs (miRNAs) are, small (roughly 19-25 nucleotides in length), conserved, non-coding, single-stranded, and functional RNA molecules with the properties of gene expression regulation through mRNA degradation, translation repression, mRNA deadenylation as well as gene silencing via histone methylation. They even have the ability to increase gene expression levels. The biogenesis of miRNAs is divided into two canonical and non-canonical pathways. The second pathway has a divergent mechanism for the biogenesis of miRNAs. miRNAs can be transcribed from specific genes or introns of protein-coding genes. A single miRNA species can control the expression of hundreds of genes, and also one gene can be the target of different miRNAs. These molecules have been identified in eukaryotic organisms such as mammals and plants and even in viruses. miRNAs play an inevitable role in the life cycle of eukaryotic cells. They are involved in any biological processes such as the regulation of cell proliferation and differentiation, apoptosis, signaling, and defense responses through their spatio-temporal expression manner. Aberrant expression of miRNAs is involved in a large number of biological disorders, which illustrates their great potential to be applied in the diagnosis and treatment of various diseases. miRNA inhibitors (anti-miRs) and artificial miRNAs (miRNA mimics) are two general approaches to balance the dysregulated miRNA levels that make it possible to treat various biological disorders. In this study, in general, the biogenesis and the role of miRNAs, the origin of miRNAs, viral miRNAs, miRNA detection procedures, in silico miRNA analysis tools, miRNA-based therapies and their obstacles, and miRNAs as potential non-invasive biomarkers are discussed. Finally, it is stated the importance of dietary miRNAs.

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MicroRNAs and osteosarcoma: Potential targets for inhibiting metastasis and increasing chemosensitivity

Cited by 24 publications

References 203 publications

DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway

DPY30 promotes the growth and survival of osteosarcoma cell by regulating the PI3K/AKT signal pathway

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

MicroRNAs; their therapeutic and biomarker properties

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