Identification of a Novel Oncogenic Fusion Gene SPON1-TRIM29 in Clinical Ovarian Cancer That Promotes Cell and Tumor Growth and Enhances Chemoresistance in A2780 Cells

Nagasawa, Saya; Ikeda, Kazuhiro; Shintani, Daisuke; Yang, Chiujung; Takeda, Satoru; Horie, Kuniko; Inoue, Satoshi

doi:10.3390/ijms23020689

Cited by 4 publications

(1 citation statement)

References 62 publications

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“…Previously predicted gene fusions in ovarian cancer transcriptomes have contributed to understanding of tumor physiology [39] . Some of these include BCAM-AKT2 (constitutive activation of AKT2 [39] , MUC1-TRIM46-KRTCAP2 and SPON1-TRIM29 (chemoresistance / therapy [40] , [41] ), URB1-C21ORF45 and CTBS-GNG5 (suppression of tumor growth, [42] , [43] ), DPP9-PPP6R3 and DPP9-PLIN3 (adverse effects on tumor suppressor functioning, [44] ), several fusions of ABCB1 and CCNL2 [45] , [46] , while CDKN2D-WDFY2, SPON1-TRIM29 and ESRRA-C11orf20 have diagnostic potential [47] , [48] ,…”

Section: Discussionmentioning

confidence: 99%

Pattern recognition in the landscape of seemingly random chimeric transcripts

Sridhar,

More,

Jadhav

et al. 2023

Computational and Structural Biotechnology Journal

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Section: Discussionmentioning

confidence: 99%

Pattern recognition in the landscape of seemingly random chimeric transcripts

Sridhar,

More,

Jadhav

et al. 2023

Computational and Structural Biotechnology Journal

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Oncogenic SLC2A11–MIF fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability

Cheng,

Yang,

et al. 2024

MedComm

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Chimeric RNAs, distinct from DNA gene fusions, have emerged as promising therapeutic targets with diverse functions in cancer treatment. However, the functional significance and therapeutic potential of most chimeric RNAs remain unclear. Here we identify a novel fusion transcript of solute carrier family 2‐member 11 (SLC2A11) and macrophage migration inhibitory factor (MIF). In this study, we investigated the upregulation of SLC2A11–MIF in The Cancer Genome Atlas cohort and a cohort of patients from Sun Yat‐Sen Memorial Hospital. Subsequently, functional investigations demonstrated that SLC2A11–MIF enhanced the proliferation, antiapoptotic effects, and metastasis of bladder cancer cells in vitro and in vivo. Mechanistically, the fusion protein encoded by SLC2A11–MIF interacted with polypyrimidine tract binding protein 1 (PTBP1) and regulated the mRNA half‐lives of Polo Like Kinase 1, Roundabout guidance receptor 1, and phosphoinositide‐3‐kinase regulatory subunit 3 in BCa cells. Moreover, PTBP1 knockdown abolished the enhanced impact of SLC2A11–MIF on biological function and mRNA stability. Furthermore, the expression of SLC2A11–MIF mRNA is regulated by CCCTC‐binding factor and stabilized through RNA N4‐acetylcytidine modification facilitated by N‐acetyltransferase 10. Overall, our findings revealed a significant fusion protein orchestrated by the SLC2A11–MIF–PTBP1 axis that governs mRNA stability during the multistep progression of bladder cancer.

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SPON1 is an independent prognostic biomarker for ovarian cancer

et al. 2023

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Background Ovarian cancer has the worst outcome among gynecological malignancies; therefore, biomarkers that could contribute to the early diagnosis and/or prognosis prediction are urgently required. In the present study, we focused on the secreted protein spondin-1 (SPON1) and clarified the prognostic relevance in ovarian cancer. Methods We developed a monoclonal antibody (mAb) that selectively recognizes SPON1. Using this specific mAb, we determined the expression of SPON1 protein in the normal ovary, serous tubal intraepithelial carcinoma (STIC), and ovarian cancer tissues, as well as in various normal adult tissues by immunohistochemistry, and verified its clinicopathological significance in ovarian cancer. Results The normal ovarian tissue was barely positive for SPON1, and no immunoreactive signals were detected in other healthy tissues examined, which was in good agreement with data obtained from gene expression databases. By contrast, upon semi-quantification, 22 of 242 ovarian cancer cases (9.1%) exhibited high SPON1 expression, whereas 64 (26.4%), 87 (36.0%), and 69 (28.5%) cases, which were designated as SPON1-low, possessed the moderate, weak, and negative SPON1 expression, respectively. The STIC tissues also possessed SPON1-positive signals. The 5-year recurrence-free survival (RFS) rate in the SPON1-high group (13.6%) was significantly lower than that in the SPON1-low group (51.2%). In addition, high SPON1 expression was significantly associated with several clinicopathological variables. Multivariable analysis revealed that high SPON1 was an independent prognostic factor for RFS of ovarian cancer. Conclusions SPON1 represents a prognostic biomarker for ovarian cancer, and the anti-SPON1 mAb could be valuable as an outcome predictor.

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Identification of a Novel Oncogenic Fusion Gene SPON1-TRIM29 in Clinical Ovarian Cancer That Promotes Cell and Tumor Growth and Enhances Chemoresistance in A2780 Cells

Cited by 4 publications

References 62 publications

Pattern recognition in the landscape of seemingly random chimeric transcripts

Pattern recognition in the landscape of seemingly random chimeric transcripts

Oncogenic SLC2A11–MIF fusion protein interacts with polypyrimidine tract binding protein 1 to facilitate bladder cancer proliferation and metastasis by regulating mRNA stability

SPON1 is an independent prognostic biomarker for ovarian cancer

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