PLXNC1

Last update 08 May 2025

Basic Info

Synonyms

CD232, plexin C1, Plexin-C1

+ [3]

Introduction

Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8 (By similarity).

100 Clinical Results associated with PLXNC1

100 Translational Medicine associated with PLXNC1

0 Patents (Medical) associated with PLXNC1

Literatures (Medical) associated with PLXNC1

01 Jan 2025·Journal of Investigative Dermatology

Identifying Potential Drug Targets for Keloid: A Mendelian Randomization Study

Article

Author: Luo, Xusong ; Wang, Yinmin ; Yuan, Zhaoqi ; Liu, Fei ; Wang, Xiuxia ; Yang, Jun

Keloids are a skin fibrosis disease characterized by troublesome symptoms, a varying degree of recurrence and inevitable side effects from treatments. Thus, identifying their drug targets is necessary. A 2-sample Mendelian randomization analysis was conducted using proteins from the intersection of the deCODE database and "The Druggable Genome and Support for Target Identification and Validation in Drug Development" as the exposure variable. The outcome variable was based on recently published GWAS of keloids. Summary data-based Mendelian randomization and colocalization analysis was employed to distinguish pleiotropy from linkage. Candidate targets underwent drug target analysis. The primary findings were validated through single-cell RNA-sequencing data, Western Blot and immunofluorescence staining on keloids. Seven proteins were identified as potential drug targets for keloids. Among these proteins, Hedgehog-interacting protein, neurotrimin [NTM], KLKB1, and CRIPTO showed positive correlations with keloids, while PLXNC1, SCG3 and PDGFD exhibited negative correlations. Combined with the single-cell RNA-sequencing data, NTM, PLXNC1, and PDGFD were found highly expressed in the fibroblasts. NTM showed a significant increase in keloids as compared to normal scars. In accordance with the analysis, higher levels of protein expression of NTM in keloids compared to normal skin was observed. The identified proteins may be appealing drug targets for keloids treatment with a special emphasis on NTM.

01 Dec 2024·Phytomedicine

EGCG targeting STAT3 transcriptionally represses PLXNC1 to inhibit M2 polarization mediated by gastric cancer cell-derived exosomal miR-92b-5p

Article

Author: Du, Yan ; Xu, Hao ; Zhou, Wence ; Ye, Zhenzhen ; Dong, Shi ; Zhang, Hui ; Yi, Jianfeng ; Wang, Tianming ; Cao, Hongtai ; Dong, Chunlu ; Li, Xin

BACKGROUNDM2-polarized tumor-associated macrophages (TAMs) predominate in tumor microenvironment (TME) and serve primary functions in tumor progression, including growth, angiogenesis, metastasis, immunosuppression, chemoresistance, and poor prognosis. The reversal of M2 polarization provides a new treatment strategy for cancer. Presently, the molecular mechanisms of M2 polarization have yet to be fully characterized, and there is a lack of effective therapeutic targets and drugs. Cancer cells initiate an immunosuppressive TME by recruiting macrophages and promoting M2 polarization through the secretion of inflammatory factors. Accordingly, blocking cancer cell-induced TAM M2 polarization may present a more effective strategy from the perspective of cancer cells. Hedyotis diffusa Willd (HDW) possesses immunomodulatory and antitumor properties, and is a precious and direct source of small molecule natural products with a dual function of inhibition of tumor growth and tumor cell-mediated M2 polarization.OBJECTIVETo identify a new target promoting gastric cancer (GC) cell growth and GC cell-mediated M2 polarization from mRNA profiles of GC cells treated with HDW injection (HDI) and to excavate a natural product from HDI that can regulate related mRNA and inhibit the aforementioned effects.METHODSRNA sequencing (RNA-seq) was used to analyze HDI-regulated differentially expressed mRNAs (HRmRNAs) in MKN45 cells. Weighted gene co-expression network analysis (WGCNA), univariate and multivariate Cox regression analysis, KM survival curves, and association analysis between HRmRNA and clinical characteristics/tumor infiltrating immune cells (TIICs) individually were utilized to screen out the target HRmRNA associated with prognosis and M2 macrophage infiltration in GC. shRNA lentiviral vectors were used for stably silencing, and transient overexpressing plasmids were constructed for overexpression. CCK8, EdU, colony formation, migration and invasion assays were used to validate the function of drugs and molecules in GC. HDI constituent analysis was performed using UHPLC-QE-MS. A network of HDI constituent-hub transcription factor (TF)-HRmRNA was constructed based on RNA-Seq, network pharmacology and TFs prediction. Exosome isolation and identification were performed using ultracentrifugation, NTA, TEM and western blot. Apoptosis and macrophage phenotypes were determined by flow cytometric analysis. Small RNA-Seq made exosomal miRNA identification. Small molecule interaction with targets were analyzed using molecular docking, SPR and CETSA. The direct relationship between transcription factors and promoters was verified using ChIP-QPCR and dual-luciferase reporter gene assay. A nude mice xenograft tumor model was established for vivo validation.RESULTSHDI inhibited MKN45 cell proliferation, migration, invasion and promoted apoptosis. RNA-Seq identified 2583 HRmRNAs. PLXNC1 was screened out as the target HRmRNA associated with prognosis and M2 macrophage infiltration in GC. PLXNC1 promoted GC cell proliferation and facilitated TAMs M2 polarization by transferring GC cell-derived exosomal miR-92b-5p, inhibiting SOCS7-STAT3 interactions and subsequently activating STAT3 in macrophages. M2 TAMs induced by PLXNC1-mediated GC cell-derived exosomes promoted GC cell migration and invasion. PLXNC1 regulated exosomal miR-92b-5p through the MEK1/MSK1/CREB1 pathway. STAT3 could transcriptionally regulate PLXNC1 expression in GC cells. The network of HDI constituent-hub TF-HRmRNA showed epigallocatechin gallate (EGCG) from HDI targeted STAT3 to transcriptionally regulate PLXNC1 expression. EGCG as a natural product directly bound to STAT3 to diminish its nuclear localization, resulting in the transcriptional repression of PLXNC1 and the reversal of M2 polarization induced by PLXNC1-mediated GC cell-derived exosomes.CONCLUSIONPLXNC1 is a novel target exerting dual effects on GC cell proliferation and GC cell-mediated M2 polarization. EGCG derived from HDI inhibits GC cell proliferation and targets STAT3 to inhibit M2 polarization induced by PLXNC1-mediated exosomes derived from GC cells, which may be a multi-target therapeutic agent for GC cell proliferation and immune microenvironment.

01 Dec 2024·Neurobiology of Disease

The ataxia-telangiectasia disease protein ATM controls vesicular protein secretion via CHGA and microtubule dynamics via CRMP5

Article

Author: Possemato, Anthony P ; Stokes, Matthew P ; Abell, Kathryn ; Auburger, Georg ; Reichlmeir, Marina ; Duecker, Ruth Pia ; Key, Jana ; Schubert, Ralf ; Röhrich, Hanna

The autosomal recessive disease ataxia-telangiectasia (A-T) presents with cerebellar degeneration, immunodeficiency, radiosensitivity, capillary dilatations, and pulmonary infections. Most symptoms outside the nervous system can be explained by failures of the disease protein ATM as a Ser/Thr-kinase to coordinate DNA damage repair. However, ATM in adult neurons has cytoplasmic localization and vesicle association, where its roles remain unclear. Here, we defined novel ATM protein targets in human neuroblastoma cells, and filtered initial pathogenesis events in ATM-null mouse cerebellum. Profiles of global proteome and phosphoproteomics - both direct ATM/ATR substrates and overall phosphorylation changes - confirmed previous findings for NBN, MRE11, MDC1, CHEK1, EIF4EBP1, AP3B2, PPP2R5C, SYN1 and SLC2A1. Even stronger downregulation of ATM/ATR substrate phosphopeptides after ATM-depletion was documented for CHGA, EXPH5, NBEAL2 and CHMP6 as key factors of protein secretion and endosome dynamics, as well as for CRMP5, DISP2, PHACTR1, PLXNC1, INA and TPX2 as neurite extension factors. Prominent effects on semaphorin-CRMP5-microtubule signals and ATM association with CRMP5 were validated. As a functional consequence, microtubules were stabilized, and neurite retraction ensued. The impact of ATM on secretory granules confirms previous ATM-null cerebellar transcriptome findings. This study provides the first link of A-T neural atrophy to growth cone collapse and aberrant microtubule dynamics.

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PLXNC1

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