Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway

Hai, Rui; You, Qian; Wu, Fei; Qiu, Guochun; Yang, Qian; Shen, Liang; Xie, Linjun; Zhou, Xiangyu

doi:10.1007/s11033-022-07220-8

Cited by 5 publications

(3 citation statements)

References 26 publications

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“…SLC5A8 codes for a transporter belonging to the Na(+)/glucose co-transporter gene family, and the protein coded by SLC5A8 can transport iodide and regulate the Na(+)-coupled and electrogenic transport of many monocarboxylates ( 39 ). Our results support our earlier observations, which showed that SEMA3D ( 40 ), CRABP1 ( 41 ), SLC5A8 ( 42 ), and SCARA5 ( 43 ) are tumor suppressor genes in PTC, while GDF15 ( 44 ), CHI3L1 ( 45 , 46 ), GABRB2 ( 47 ), and ARHGAP36 ( 48 ) are oncogenic genes in PTC. However, very little research has been conducted on the roles of B3GNT3 , TMPRSS6 , CLDN16 , MFAP4 , MYOC , C7 , APOD , SLIT1 , TMEM215 , and IGSF1 in PTC.…”

Section: Discussionsupporting

confidence: 92%

Identification and validation of subclusters of papillary thyroid carcinoma based on Human Phenotype Ontology

Xuan¹,

Hu²,

Xu³

et al. 2023

Gland Surg

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Background The increase in the diagnosis of papillary thyroid carcinoma (PTC) has prompted researchers to establish a diagnostic model and identify functional subclusters. The Human Phenotype Ontology (HPO) platform is widely available for differential diagnostics and phenotype-driven investigations based on next-generation sequence-variation data. However, a systematic and comprehensive study to identify and validate PTC subclusters based on HPO is lacking. Methods We first used the HPO platform to identify the PTC subclusters. An enrichment analysis was then conducted to examine the key biological processes and pathways associated with the subclusters, and a gene mutation analysis of the subclusters was conducted. For each subcluster, the differentially expressed genes (DEGs) were selected and validated. Finally, a single-cell RNA-sequencing data set was used to verify the DEGs. Results In our study, 489 PTC patients from The Cancer Genome Atlas (TCGA) were included. Our analysis demonstrated that distinct subclusters of PTC are associated with different survival times and have different functional enrichment, and that C-C motif chemokine ligand 21 ( CCL21 ) and zinc finger CCHC-type containing 12 ( ZCCHC12 ) were the common down- and upregulated genes, respectively, in the 4 subclusters. Additionally, 20 characteristic genes were identified in the 4 subclusters, some of which have previously been reported to have roles in PTC. Further, we found that these characteristic genes were mainly expressed in thyrocytes, endothelial cells, and fibroblasts, and were rarely expressed in immune cells. Conclusions We first identified subclusters in PTC based on HPO and found that patients with distinct subclusters have different prognoses. We then identified and validated the characteristic genes in the 4 subclusters. These findings are expected to serve as a crucial reference that will improve our understanding of PTC heterogeneity and the use of novel targets.

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Section: Discussionsupporting

confidence: 92%

Identification and validation of subclusters of papillary thyroid carcinoma based on Human Phenotype Ontology

Xuan¹,

Hu²,

Xu³

et al. 2023

Gland Surg

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“…Notably, previous studies also revealed involvement in carcinogenesis and potential mechanisms of Sema3D. Although one study indicated that samples of bladder cancer downregulated by Sema3D had a good overall survival prognosis [ 22 ], more studies tended toward the tumor suppressive role of Sema3D by experiment validation [ 23 , 24 ]. However, the Sema3D protein expression and potential mechanisms have not been investigated in ccRCC and remained unclear.…”

Section: Discussionmentioning

confidence: 99%

Transmembrane Transporter Sema3D Serves as a Tumor Suppressor in Localized Clear Cell Renal Cell Carcinoma

Xie

Shang

et al. 2022

Journal of Oncology

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Background. The transmembrane transporter Sema3D is a vital molecule involved in axon guidance and carcinogenesis of variant malignancies. However, the relationship between Sema3D and clear cell renal cell carcinoma (ccRCC) is barely reported and remains unclear. Methods. Sema3D expression and the connection of clinical and histological characteristics were first analyzed with transcriptome data in the TCGA repository. We then located and examined the Sema3D expression in ccRCC patients by using immunofluorescence staining in the tissue microarray. The prognostic value of Sema3D in localized ccRCC was evaluated by Cox proportional hazard analysis. Functional and gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to describe the potential mechanisms of Sema3D in ccRCC. Correlation analysis between Sema3D and tumor-infiltrating lymphocytes was calculated by ssGSEA. Results. In 86 ccRCC patients, Sema3D mRNA and protein expression were downregulated in tumor tissues than the para-tumor tissues, and Sema3D was dominantly expressed in the extracellular space. Low expression of Sema3D was associated with advanced tumor stage, advanced histological grade, and poor prognosis in ccRCC. In the subgroup analysis of 81 localized ccRCC patients, Sema3D expression level was an independent protective prognostic factor for overall survival (OS) (HR = 0.125, p = 0.043 ). Coagulation, complement, estrogen response, and KRAS signaling hallmark gene sets were identified as Sema3D-related signaling pathways. The expression level of Sema3D was significantly correlated with a high abundance of several immune cells (neutrophils, eosinophils, and T helper cells). Conclusions. Transmembrane transporter Sema3D is an efficient prognostic biomarker for localized ccRCC patients, by playing the role of tumor suppressor in ccRCC. Sema3D can be a novel therapeutic target for ccRCC.

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“…In the cellular contexts, activation of Nrp receptors promotes MAPK signaling, with Sema3 family ligands being required for MAPK activation (Wey et al, 2005;Bechara et al, 2008;Fung et al, 2016;Hai et al, 2022). Since I observed a potential requirement of the Nrp-Sema3d signal in pouch formation, I next examined whether MAPK was necessary in the endoderm for pouch development.…”

Section: Development Of Pouches Requires Mitogen-activated Protein Ki...mentioning

confidence: 99%

A Feasible Role of Neuropilin Signaling in Pharyngeal Pouch Formation in Zebrafish

Choe

2023

Dev. Reprod.

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Pharyngeal pouches are an important epithelial structure controlling facial skeletal development in vertebrates. A series of pouches arise sequentially in the pharyngeal endoderm through collective cell migration followed by rearrangement of pouch-forming cells. While crucial transcription factors and signaling molecules have been identified in pouch formation, a role for Neuropilins (Nrps) in pouch development has not yet been analyzed in any vertebrates. Nrps are cell surface receptors essential for angiogenesis and axon guidance. In all vertebrates, the two Nrp family members, Nrp1 and Nrp2, are conserved in the genome, with two paralogs for Nrp1 (Nrp1a and Nrp1b) and Nrp2 (Nrp2a and Nrp2b) being identified in zebrafish. Here, I report a potential requirement of Nrp signaling in pouch development in zebrafish. nrp1a and nrp2b were expressed in the developing pouches, with sema3d, a ligand for Nrps, being expressed in the pouches. Knocking down Nrps signaling in the pharyngeal endoderm led to severe defects in pouches and facial cartilages. In addition, blocking Mitogen-activated protein kinase (MAPK) activities, a downstream effector of Nrp signaling, in the pharyngeal endoderm caused similar defects in pouches and facial skeleton to those by knocking down Nrps signaling. My results suggest that Nrp signaling acts for pouch formation through MAPK.

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Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway

Cited by 5 publications

References 26 publications

Identification and validation of subclusters of papillary thyroid carcinoma based on Human Phenotype Ontology

Identification and validation of subclusters of papillary thyroid carcinoma based on Human Phenotype Ontology

Transmembrane Transporter Sema3D Serves as a Tumor Suppressor in Localized Clear Cell Renal Cell Carcinoma

A Feasible Role of Neuropilin Signaling in Pharyngeal Pouch Formation in Zebrafish

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