Although it is a leading cause of cancer-related mortality among women globally, breast cancer (BC) has drawn increased attention owing to its poor prognosis and the challenges associated with limited treatment options. SLC35A2 was shown to be dysregulated in a number of tumor types according to multiple investigations. However, its function in BC was rarely reported. This study aims to investigate the expression of SLC35A2 in BC and its impact on the functionality and prognosis of BC cells. We collected 11 pairs of BC tissues and normal specimens, obtaining clinical information from 1,118 BC patients through RNA sequencing analysis. Different BC cell lines were used in experiments, and the roles of SLC35A2 in cell proliferation, invasion, and migration was assessed through gene silencing and functional assays. Additionally, a prognostic model, including SLC35A2 expression levels, age, T-stage, M-stage, N-stage, and clinical stage, was constructed, and its predictive performance in overall survival was validated using time-dependent receiver operating characteristic curves. High SLC35A2 expression was correlated positively with patient age and T-stage. Kaplan-Meier survival curves and Cox regression analysis confirmed the independent and significant prognostic value of SLC35A2 in overall survival. Functional experiments demonstrated that SLC35A2 silencing inhibited the proliferation, migration, and invasion of BC cells, affecting their metastatic potential through modulation of the Wnt/β-catenin/EMT signaling pathway. In conclusion, our study reveals the crucial role of SLC35A2 in BC, providing a novel biomarker for clinical management and valuable insights into the underlying mechanisms of BC pathogenesis.

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http://dx.doi.org/10.1038/s41598-024-84584-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695858PMC

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Although it is a leading cause of cancer-related mortality among women globally, breast cancer (BC) has drawn increased attention owing to its poor prognosis and the challenges associated with limited treatment options. SLC35A2 was shown to be dysregulated in a number of tumor types according to multiple investigations. However, its function in BC was rarely reported.

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ILAE genetic literacy series: Focal cortical dysplasia.

Epileptic Disord

December 2024

Department of Neurology, The Royal Children's Hospital, Parkville, Victoria, Australia.

Focal cortical dysplasia (FCD) is a common cause of drug-resistant focal epilepsy in children and young adults and is often surgically remediable. The genetics of FCD are increasingly understood due to the ability to perform genomic testing including deep sequencing of resected FCD tissue specimens. There is clear evidence that FCD type II occurs secondary to both germline and somatic mTOR pathway variants, while emerging literature supports the role of SLC35A2, a glycosylation gene, in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE).

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Lesional focal epilepsy (LFE) is a common and severe seizure disorder caused by epileptogenic lesions, including malformations of cortical development (MCD) and low-grade epilepsy-associated tumors (LEAT). Understanding the genetic etiology of these lesions can inform medical and surgical treatment. We conducted a somatic variant enrichment mega-analysis in brain tissue from 1386 individuals who underwent epilepsy surgery, including 599 previously unpublished individuals with ultra-deep ( > 1600x) targeted panel sequencing.

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Article Synopsis
  • * A pathogenic variant was found in 31% of the total cases analyzed, with higher rates in specific conditions like focal cortical dysplasia type II (33%) and hemimegalencephaly (62%), particularly involving the mTOR signaling pathway.
  • * The identification of germline and somatic variants, especially in focal epilepsy genes, provides insights for future analyses on genetic factors related to surgical outcomes, which could enhance patient counseling and treatment plans.
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Objective: Brain somatic variants in SLC35A2 were recently identified as a genetic marker for mild malformations of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE). The role of SLC35A2 in cortical development and the contributions of abnormal neurons and oligodendrocytes to seizure activity in MOGHE remain largely unexplored.

Methods: Here, we generated a novel Slc35a2 floxed allele, which we used to develop two Slc35a2 conditional knockout mouse lines targeting (1) the Emx1 dorsal telencephalic lineage (excitatory neurons and glia) and (2) the Olig2 lineage (oligodendrocytes).

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