Chondrocyte-derived Exosomal miR-195 Inhibits Osteosarcoma Cell Proliferation and Anti-Apoptotic by Targeting KIF4A in vitro and in vivo

Lu, Yao; Cao, Gaolu; Lan, Haiying; Liao, Hua; Hu, Yue; Feng, Hailan; Liu, Xiaojian; Huang, Panpan

doi:10.1016/j.tranon.2021.101289

Cited by 12 publications

(11 citation statements)

References 44 publications

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“…We found that KIF4A can reverse the inhibitory effect of miR‐379‐5p on BC cell migration, invasion, and proliferation. Similar studies have shown that exosomal miR‐195 inhibited osteosarcoma cell proliferation and antiapoptosis in vitro, inhibited tumor growth in vivo, and reduced tolerance to chemotherapeutic drugs by targeting KIF4A 36 . These results suggest that miR‐379‐5p inhibits BC progression by downregulating KIF4A.…”

Section: Discussionsupporting

confidence: 69%

MiR‐379‐5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A

Yang

Jia

et al. 2022

Thoracic Cancer

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Background Many studies have shown that microRNAs (miRNAs) play an essential role in gene regulation and tumor development. This study aimed to explore the expression of miR‐379‐5p and its mechanisms of affecting proliferation, migration, and invasion in breast cancer (BC). Methods MiRNAs and mRNAs expression data of BC and normal breast tissue samples were downloaded from the TCGA and GEO databases. qRT‐PCR was used to detect the expression of miR‐379‐5p in human normal breast epithelial cell lines and human BC cell lines. The proliferation ability of transfected cells was detected by colony formation and EdU assays. The mobility and invasion ability of transfected cells was measured by wound healing and transwell assays. The relative protein expression of transfected cells was detected by western blot. Dual luciferase reporter assay was performed to identify the targeted binding of miR‐379‐5p and KIF4A. Results MiR‐379‐5p was lowly expressed in BC tissue samples and BC cell lines. The target genes of miR‐379‐5p were involved in many cancer‐related signaling pathways. PPI analysis and the cytoHubba algorithm of Cytoscape identified 10 genes as the hub genes. Survival analysis showed that only KIF4A expression in 10 hub genes was significantly associated with the prognosis of BC patients and was significantly upregulated in BC. Overexpression of miR‐379‐5p inhibited proliferation, migration, and invasion in the BC cell line MDA‐MB‐231, which could be reversed by KIF4A. Conclusions MiR‐379‐5p inhibits proliferation, migration, and invasion of BC by targeting KIF4A.

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Section: Discussionsupporting

confidence: 69%

MiR‐379‐5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A

Yang

Jia

et al. 2022

Thoracic Cancer

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“…Early detection and treatment of osteosarcoma patients cannot be overstated [ 16 ]. It has an early onset age, a high malignancy, a high rate of metastasis, and a bad prognosis [ 17 ]. Its proclivity for metastasizing is the most common cause of therapy failure and poor prognosis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

DNMT3A Regulates miR-149 DNA Methylation to Activate NOTCH1/Hedgehog Pathway to Promote the Development of Junctional Osteosarcoma

Cheng

Wang

2022

BioMed Research International

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Purpose. To investigate the DNMT3A/miR-149/NOTCH1/Hedgehog axis regulating the development of osteosarcoma. Methods. First, microRNA and mRNA expression microarrays were downloaded from the GEO database for osteosarcoma and differentially expressed microRNAs were analyzed. Subsequently, we collected cancerous tissues and corresponding paracancerous tissues from 42 osteosarcoma patients and examined the expression levels of miR-149, DNMT3A, and NOTCH1 in the samples. Subsequently, miR-149 was overexpressed in osteosarcoma cells to detect cell proliferation and metastatic ability changes. We then queried the methylation level of the miR-149 promoter on the bioinformatics website and verified it by experiment. We further demonstrated the expression level of miR-149 with NOTCH1 using a dual luciferase assay and confirmed the role of NOTCH1 on osteosarcoma cell growth and metastasis by functional rescue assay. Finally, we detected the activation level of the Hedgehog/catenin signaling pathway by WB and immunofluorescence. Results. miR-149 was significantly low expressed in osteosarcoma tissues and cells, while DNMT3A and NOTCH1 were highly expressed in osteosarcoma tissues and cells, and negatively correlated with miR-149 expression levels. Overexpression of miR-149 significantly inhibited the growth and metastasis of osteosarcoma cells in vitro and in vivo, and we found that DNMT3A could promote the methylation modification of the miR-149 promoter, thereby inhibiting the expression of miR-149. Subsequently, the experimental results showed that miR-149 could target negative regulation of NOTCH1, and further overexpression of NOTCH1 in cells with high miR-149 expression could promote the growth and metastasis of osteosarcoma cells in vitro. Conclusion. The methyltransferase DNMT3A suppresses miR-149 expression by promoting methylation modification of the miR-149 promoter, resulting in elevated expression levels of NOTCH1 in cells, therefore exacerbating activation of the Hedgehog signaling pathway and therefore exacerbating the development and progression of osteosarcoma.

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“…Cells at the logarithmic growth phase were seeded in a 6-well plate and grown to 30%–50% confluence. Subsequently, the cells were transfected with overexpression plasmid DNA, short hairpin RNA (shRNA), or empty vectors (pLVX) (the aforementioned plasmids had all been purchased from GenePharma, Shanghai, China) using Lipofectamine 3000 (Invitrogen) according to the manufacturer’s instructions [20] . The gene silencing efficiency of the shRNA was confirmed using quantitative real-time polymerase chain reaction (qRT-PCR).…”

Section: Methodsmentioning

confidence: 99%

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

Lu¹,

Huang²,

Li³

et al. 2023

ABBS

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Background: Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents.In clinical treatments, the insensitivity of OS to conventional radiotherapy regimens signi cantly contributes to poor patient prognosis and survival. EXO1 is responsible for DNA repair pathways and telomere maintenance. Meanwhile, ATM and ATR are considered switches as they can regulate the expression of EXO1. However, their expression and interaction in OS cells under irradiation (IR) remains unclear. This study aimed to investigate the roles of FBXO32, ATM, ATR and EXO1 in OS radiotherapy insensitivity and poor patient prognosis and explore potential pathogenic mechanisms. Methods: Bioinformaticsmethods were employed to analyze differential gene expression and the correlations with prognosis in OS. Cell counting kit 8 assays, clone formation assays, and ow cytometry were used to evaluate cell survivaland apopotosisunder IR. Co-IP assays detected protein-protein interactions. Results: Bioinformatics analysis revealed that EXO1 is closely related to the survival, apoptosis and poorer prognosis in OS. The silencingof EXO1 suppressed cell proliferation and increased the sensitivity of OS cells. Molecular biological experiments showed that the ATMand ATR acted as the switch to regulate EXO1 expression under IR. Conclusion: Higher expression of EXO1, which was closely correlated with IR insensitivity and poorer prognosis, might be used as a prognostic indicator for OS. Phosphorylated-ATM enhanced the expression of EXO1, and phosphorylated-ATR induced the degradation of EXO1. More importantly, FBXO32 degraded ATR via ubiquitination in time dependent. Our data may provide a reference for future research on mechanisms, clinical diagnosis, and treatment of OS.

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Chondrocyte-derived Exosomal miR-195 Inhibits Osteosarcoma Cell Proliferation and Anti-Apoptotic by Targeting KIF4A in vitro and in vivo

Cited by 12 publications

References 44 publications

MiR‐379‐5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A

MiR‐379‐5p inhibits the proliferation, migration, and invasion of breast cancer by targeting KIF4A

DNMT3A Regulates miR-149 DNA Methylation to Activate NOTCH1/Hedgehog Pathway to Promote the Development of Junctional Osteosarcoma

The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression

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