The Regulatory Role of PRRX1 in Cancer Epithelial-Mesenchymal Transition

Du, Wenjiao; Liu, Xinchang; Yang, Man; Wang, Weipeng; Sun, Jing

doi:10.2147/ott.s316102

Cited by 11 publications

(9 citation statements)

References 36 publications

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“…Several studies suggested the role of PRRX1 in the regulation of tumor progression and metastasis through the regulation of the EMT, and acting as a ETM-TF that regulates stemness activity and EMT plasticity in TME (17,43). The PRRX1 isoform PRRX1A was found to play important roles in regulating the metastatic potential and stemness of lung cancer (44), a finding supported by the results of our pan-cancer analysis.…”

Section: Discussionsupporting

confidence: 85%

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

Meng

Chen

et al. 2022

Front. Immunol.

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Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UM develops and is sustained by inflammation and immunosuppression from the tumor microenvironment (TME). This study sought to identify a reliable TME-related biomarker that could provide survival prediction and new insight into therapy for UM patients. Based on clinical characteristics and the RNA-seq transcriptome data of 80 samples from The Cancer Genome Atlas (TCGA) database, PRRX1 as a TME- and prognosis-related gene was identified using the ESTIMATE algorithm and the LASSO–Cox regression model. A prognostic model based on PRRX1 was constructed and validated with a Gene Expression Omnibus (GEO) dataset of 63 samples. High PRRX1 expression was associated with poorer overall survival (OS) and metastasis-free survival (MFS) in UM patients. Comprehensive results of the prognostic analysis showed that PRRX1 was an independent and reliable predictor of UM. Then the results of immunological characteristics demonstrated that higher expression of PRRX1 was accompanied by higher expression of immune checkpoint genes, lower tumor mutation burden (TMB), and greater tumor cell infiltration into the TME. Gene set enrichment analysis (GSEA) showed that high PRRX1 expression correlated with angiogenesis, epithelial–mesenchymal transition (EMT), and inflammation. Furthermore, downregulation of PRRX1 weakened the process of EMT, reduced cell invasion and migration of human UM cell line MuM-2B in vitro. Taken together, these findings indicated that increased PRRX1 expression is independently a prognostic factor of poorer OS and MFS in patients with UM, and that PRRX1 promotes malignant progression of UM by facilitating EMT, suggesting that PRRX1 may be a potential target for UM therapy.

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Section: Discussionsupporting

confidence: 85%

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

Meng

Chen

et al. 2022

Front. Immunol.

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“…PRRX1 mediates cancer cell invasion and metastasis by starting EMT ( Meng et al, 2022 ). In addition, PRRX1 impacts the division and metastasis of various tumor cells via Wnt/β-catenin and Notch pathways, and maintains the characteristics of tumor stem cells to promote EMT ( Du et al, 2021 ). A disintegrin and metalloprotease12 (ADAM12) is implied in the starting and advancement of many tumors.…”

Section: Discussionmentioning

confidence: 99%

Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma

et al. 2023

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Background: Uveal melanoma (UM) is the most frequent ocular neoplasm with a strong metastatic ability. The prognostic value of metastasis-associated genes (MAGs) of UM remains unclear. It is urgent to develop a prognostic score system according to the MAGs of UM.Methods: Unsupervised clustering was used to identify MAGs-based molecular subtypes. Cox methods were utilized to generate a prognostic score system. The prognostic ability of the score system was detected by plotting ROC and survival curves. The immune activity and underlying function were depicted by CIBERSORT GSEA algorithms.Results: Gene cluster analysis determined two MAGs-based subclusters in UM, which were remarkably different in clinical outcomes. A risk score system containing six MAGs (COL11A1, AREG, TIMP3, ADAM12, PRRX1 and GAS1) was set up. We employed ssGSEA to compare immune activity and immunocyte infiltration between the two risk groups. Notch, JAK/STAT and mTOR pathways were greatly enriched in the high-risk group. Furthermore, we observed that knockdown of AREG could inhibit UM proliferation and metastasis by in vitro assays.Conclusion: The MAGs-based subtype and score system in UM can enhance prognosis assessment, and the core system provides valuable reference for clinical decision-making.

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“… † mRNAs encoding the following proteins: BMI1 encodes BMI1 Proto-Oncogene, Polycomb Ring Finger; BTG1 is a tumor suppressor gene that codes for BTG Anti-Proliferation Factor 1; EGR2 is a tumor suppressor gene that codes for transcription factor Early Growth Response 2; GLS encodes GLS1 (Glutaminase) which promotes proliferation as opposed to proliferation-inhibiting GLS2 (Kim and Kim 2013 ); GRIA3 encodes Glutamate Ionotropic Receptor AMPA Type Subunit 3; HK2 encodes Hexokinase 2 catalyzing the rate-limiting step of glucose metabolism and is highly expressed in rapidly growing cancer cells; ING4 encodes tumor suppressor protein that can bind p53; MSI1 encodes Musashi RNA-binding protein that is involved in tumorigenesis; MYC encodes transcription factor MYC Proto-Oncogene (c-Myc); MYO6 encodes motor protein Myosin VI; PFN1 encodes Profilin 1 that binds actin monomers and mediates actin polymerization but also inhibit formation of IP3 from PIP2; PDCD4 encodes programmed cell death protein 4 acting as a tumor suppressor; PRRX1 codes for Paired Related Homeobox 1 protein that can promote the EMT process in cancer cells (Du et al 2021 ); RASSF1A is a tumor suppressor gene encoding Ras Association Domain Family Member 1; RIPK4 encodes Receptor Interacting Serine/Threonine Kinase 4 and acts as a tumor suppressor or promoter depending on the type of cancer (Xu et al 2020c ); SLC7A11 encodes Cystine/Glutamate Transporter (Koppula et al 2021 ); TRA2B is an oncogene encoding Transformer 2 β Homolog …”

Section: Mirnas Targeting Tyms Mrnamentioning

confidence: 99%

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Matuszyk

2022

Mol Med

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Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

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The Regulatory Role of PRRX1 in Cancer Epithelial-Mesenchymal Transition

Cited by 11 publications

References 36 publications

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

PRRX1 Is a Novel Prognostic Biomarker and Facilitates Tumor Progression Through Epithelial–Mesenchymal Transition in Uveal Melanoma

Integrated single-cell and transcriptome sequencing analyses develops a metastasis-based risk score system for prognosis and immunotherapy response in uveal melanoma

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

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