Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs

Fatema, Kaniz; Larson, Zachary; Barrott, Jared J.

doi:10.32604/biocell.2022.020141

Cited by 2 publications

(2 citation statements)

References 171 publications

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“…In contrast, the EMT‐directed invasive growth of tumour cells was closely associated with enhanced aerobic glycolysis 26 . Epithelial cells acquired the capacity to migrate and invade through EMT, while losing their cell polarity and intercellular adhesive ability 1,27,28 . EMT is linked to a complex metabolic reprogramming process controlled by transcription factors specific to EMT that support higher energy needs for growth and motility in challenging environments 29 .…”

Section: Discussionmentioning

confidence: 99%

“… 26 Epithelial cells acquired the capacity to migrate and invade through EMT, while losing their cell polarity and intercellular adhesive ability. 1 , 27 , 28 EMT is linked to a complex metabolic reprogramming process controlled by transcription factors specific to EMT that support higher energy needs for growth and motility in challenging environments. 29 The silencing of metabolic genes activates EMT, demonstrating that EMT and glycolytic reprogramming are intertwined.…”

Section: Discussionmentioning

confidence: 99%

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Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo

Zhang,

Li,

Zhang

et al. 2024

J Cellular Molecular Medi

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As oncogenes or oncogene suppressors, long‐stranded non‐coding RNAs are essential for the formation and progression of human tumours. However, the mechanisms behind the regulatory role of RNA HOXA11‐AS in prostate cancer (PCa) are unclear. PCa is a common malignant tumour worldwide, and an increasing number of studies have focused on its metabolic profile. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumours. However, the role of HOXA11‐AS in PCa is unclear. This work aimed to determine how HOXA11‐AS regulated PCa in vitro and in vivo. We first explored the clinical role of HOXA11‐AS in PCa using bioinformatics methods, including single sample gene set enrichment analysis (ssGSEA), weighted gene co‐expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)‐logistics systematically. In this study, PCa cell lines were selected to assess the PCa regulatory role of HOXA11‐AS overexpression versus silencing in vitro, and tumour xenografts were performed in nude mice to assess tumour suppression by HOXA11‐AS silencing in vivo. HOXA11‐AS expression was significantly correlated with clinicopathological factors, epithelial‐mesenchymal transition (EMT) and glycolysis. Moreover, key genes downstream of HOXA11‐AS exhibited good clinical diagnostic properties for PCa. Furthermore, we studied both in vitro and in vivo effects of HOXA11‐AS expression on PCa. Overexpression of HOXA11‐AS increased PCa cell proliferation, migration and EMT, while silencing HOXA11‐AS had the opposite effect on PCa cells. In addition, multiple metabolites were downregulated by silencing HOXA11‐AS via the glycolytic pathway. HOXA11‐AS silencing significantly inhibited tumour development in vivo. In summary, silencing HOXA11‐AS can inhibit PCa by regulating glucose metabolism and may provide a future guidance for the treatment of PCa.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo

Zhang,

Li,

Zhang

et al. 2024

J Cellular Molecular Medi

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Arid1a Loss Enhances Disease Progression in a Murine Model of Osteosarcoma

Fatema,

Wang,

Pavek

et al. 2024

Cancers

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Osteosarcoma is an aggressive bone malignancy, molecularly characterized by acquired genome complexity and frequent loss of TP53 and RB1. Obtaining a molecular understanding of the initiating mutations of osteosarcomagenesis has been challenged by the difficulty of parsing between passenger and driver mutations in genes. Here, a forward genetic screen in a genetic mouse model of osteosarcomagenesis initiated by Trp53 and Rb1 conditional loss in pre-osteoblasts identified that Arid1a loss contributes to OS progression. Arid1a is a member of the canonical BAF (SWI/SNF) complex and a known tumor suppressor gene in other cancers. We hypothesized that the loss of Arid1a increases the rate of tumor progression and metastasis. Phenotypic evaluation upon in vitro and in vivo deletion of Arid1a validated this hypothesis. Gene expression and pathway analysis revealed a correlation between Arid1a loss and genomic instability, and the subsequent dysregulation of genes involved in DNA DSB or SSB repair pathways. The most significant of these transcriptional changes was a concomitant decrease in DCLRE1C. Our findings suggest that Arid1a plays a role in genomic instability in aggressive osteosarcoma and a better understanding of this correlation can help with clinical prognoses and personalized patient care.

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Navigating the genomic instability mine field of osteosarcoma to better understand implications of non-coding RNAs

Cited by 2 publications

References 171 publications

Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo

Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo

Arid1a Loss Enhances Disease Progression in a Murine Model of Osteosarcoma

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