Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis

Trang, Nguyen Thi Nha; Lai, Chao-Yang; Tsai, Hsiao‐Chi; Huang, Yuan‐Li; Liu, Shan‐Chi; Tsai, Cheng-Han; Fong, Yi‐Chin; Tzeng, Huey‐En; Tang, Chih-Hsin

doi:10.7150/ijbs.77688

Cited by 11 publications

(10 citation statements)

References 75 publications

(87 reference statements)

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“…This leads to receptor internalization and activation of intracellular signaling cascades, including MAPK pathways such as ERK and p38 MAPK ( Wang et al, 2022 ). The Apelin signaling pathway can regulate gene expression ( Trang et al, 2023 ), cell proliferation ( Chaves-Almagro et al, 2022 ), and differentiation ( Sisli et al, 2023 ), and is involved in the regulation of cardiovascular function, angiogenesis, fluid homeostasis, and energy metabolism ( Respekta et al, 2022 ; Sisli et al, 2023 ). In the present study, genes significantly enriched in the Apelin signaling pathway included APLN , which encodes the Apelin protein.…”

Section: Discussionmentioning

confidence: 99%

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation

Xu,

Yan,

Jin

et al. 2024

Front. Genet.

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DNMT3A participates in de novo methylation, yet its impact on the proliferation of testicular Sertoli cells remains unclear. Development-specific methylation has been proven to be associated with cellular development. Therefore, in this study, we simulated DNMT3A expression pattern during testicular development by DNMT3A interference. Then, RRBS and RNA-seq were used to decipher DNMT3A regulatory mechanisms on Sertoli cell proliferation. Immunofluorescence staining revealed the expression of DNMT3A in the Sertoli cells of the prepubertal testis. DNMT3A was demonstrated to inhibit the cell cycle and proliferation of Sertoli cells, while promoting cell apoptosis. After transfected with DNMT3A interference, a total of 560 DEGs and 2,091 DMGs produced by DNMT3A interference were identified between two treated groups, respectively. Integrating the results from RRBS and RNA-seq, the overlapping genes between DMGs and DEGs were found to be enriched in the Gene Ontology (GO) terms related to cellular development and the Apelin signaling pathway. The present study demonstrated the impact of DNMT3A on the proliferation of porcine testicular Sertoli cells, suggesting that DNMT3A primarily acts through the Apelin signaling pathway. These findings provide valuable insights into how DNMT3A influences testicular development and health, offering new perspectives.

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Section: Discussionmentioning

confidence: 99%

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation

Xu,

Yan,

Jin

et al. 2024

Front. Genet.

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“…Treatment and prognosis are impacted by invasion and distant metastases in BCa patients [ 31 ]. For patients with metastatic uroepithelial carcinoma, platinum-based chemotherapy is recommended as the first-line standard of care, provided they are suitable for treatment with cisplatin or carboplatin.…”

Section: Discussionmentioning

confidence: 99%

GREM1 is a potential biomarker for the progression and prognosis of bladder cancer

Jiang,

Xu,

Ning

et al. 2023

World J Surg Onc

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Background Gremlin-1 (GREM1) is a protein closely related to tumor growth, although its function in bladder cancer (BCa) is currently unknown. Our first objective was to study the GREM1 treatment potential in BCa. Methods BCa tissue samples were collected for the detection of GREM1 expression using Western blot analysis and Immunofluorescence staining. Association of GREM1 expression with clinicopathology and prognosis as detected by TCGA (The Cancer Genome Atlas) database. The functional investigation was tested by qRT-PCR, western blot analysis, CCK-8, cell apoptosis, wound healing, and transwell assays. The interaction between GREM1 and the downstream PI3K/AKT signaling pathway was assessed by Western blot analysis. Results GREM1 exhibited high expression in BCa tissues and was linked to poor prognosis. Stable knockdown of GREM1 significantly inhibited BCa cell (T24 and 5637) proliferation, apoptosis, migratory, invasive, as well as epithelial-mesenchymal transition (EMT) abilities. GREM1 promotes the progression in BCa via PI3K/AKT signaling pathway. Conclusion Findings demonstrate that the progression-promoting effect of GREM1 in BCa, providing a novel biomarker for BCa-targeted therapy.

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“…Transcriptome profiles of osteosarcoma were accessed using the TCGA database via the GDC data portal (https://portal.gdc.cancer.gov/). RNA-Seq analysis was performed on 88 osteosarcoma samples to derive gene expression profiles of the neurotrophin family and tropomyosin receptor kinase (TRK) [29].…”

Section: Materials and Methods Analysis Of Mrna Expression Profiles F...mentioning

confidence: 99%

Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib

Hou,

Chen,

Lin

2024

Cell Death Dis

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Osteosarcoma (OS) therapy presents numerous challenges, due largely to a low survival rate following metastasis onset. Nerve growth factor (NGF) has been implicated in the metastasis and progression of various cancers; however, the mechanism by which NGF promotes metastasis in osteosarcoma has yet to be elucidated. This study investigated the influence of NGF on the migration and metastasis of osteosarcoma patients (88 cases) as well as the underlying molecular mechanisms, based on RNA-sequencing and gene expression data from a public database (TARGET-OS). In osteosarcoma patients, the expression of NGF was significantly higher than that of other growth factors. This observation was confirmed in bone tissue arrays from 91 osteosarcoma patients, in which the expression levels of NGF and matrix metallopeptidase-2 (MMP-2) protein were significantly higher than in normal bone, and strongly correlated with tumor stage. In summary, NGF is positively correlated with MMP-2 in human osteosarcoma tissue and NGF promotes osteosarcoma cell metastasis by upregulating MMP-2 expression. In cellular experiments using human osteosarcoma cells (143B and MG63), NGF upregulated MMP-2 expression and promoted wound healing, cell migration, and cell invasion. Pre-treatment with MEK and ERK inhibitors or siRNA attenuated the effects of NGF on cell migration and invasion. Stimulation with NGF was shown to promote phosphorylation along the MEK/ERK signaling pathway and decrease the expression of microRNA-92a-1-5p (miR-92a-1-5p). In in vivo experiments involving an orthotopic mouse model, the overexpression of NGF enhanced the effects of NGF on lung metastasis. Note that larotrectinib (a tropomyosin kinase receptor) strongly inhibited the effect of NGF on lung metastasis. In conclusion, it appears that NGF promotes MMP-2-dependent cell migration by inhibiting the effects of miR-92a-1-5p via the MEK/ERK signaling cascade. Larotrectinib emerged as a potential drug for the treatment of NGF-mediated metastasis in osteosarcoma.

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Apelin promotes osteosarcoma metastasis by upregulating PLOD2 expression via the Hippo signaling pathway and hsa_circ_0000004/miR-1303 axis

Cited by 11 publications

References 75 publications

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation

Integration of RRBS and RNA-seq unravels the regulatory role of DNMT3A in porcine Sertoli cell proliferation

GREM1 is a potential biomarker for the progression and prognosis of bladder cancer

Targeting nerve growth factor-mediated osteosarcoma metastasis: mechanistic insights and therapeutic opportunities using larotrectinib

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