LSD1: a viable therapeutic target in cutaneous squamous cell carcinoma?

Egolf, Shaun; Capell, Brian C.

doi:10.1080/14728222.2020.1762175

Cited by 8 publications

(5 citation statements)

References 72 publications

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“…CSCC is an immense clinical and economic problem given its incidence has increased over 200% in the last three decades ( 25 , 26 ). The mortality of high-risk and metastatic CSCC is 40% within 3 years ( 27 ).…”

Section: Discussionmentioning

confidence: 99%

lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

2021

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Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) are essential for the progression of tumors, including cutaneous squamous cell carcinoma (CSCC). The present study aimed to examine the competing endogenous RNA (ceRNA) network in CSCC. Differentially expressed genes in CSCC were analyzed using the GSE66359 microarray data set, and the upstream miRNAs and lncRNAs were predicted using online database analysis (TargetScan 7.1, mirDIP 4.1, miRSearch V3.0, miRDB and RNA22 2.0) and were verified in clinical tissues. RNA pull-down and dual luciferase reporter gene assays were used to verify the targeting relationships among lncRNA human histocompatibility leukocyte antigen complex P5 (HCP5), miR-138-5p and enhancer of zeste homolog 2 (EZH2). Cell lines with a high and low HCP5 expression were screened, and a pcDNA-3.1-HCP5 overexpression vector, small interfering RNA against HCP5, miR-138-5p mimics and miR-138-5p inhibitors were transfected into the CSCC cells. Cell viability, invasion, migration, apoptotic rate and autophagy were evaluated. The effects of HCP5 on autophagy and apoptosis of CSCC cells were verified in vivo using Ki67 and TUNEL staining. EZH2 was demonstrated to be upregulated in CSCC cells. miR-138-5p target sequences were identified in HCP5 and EZH2. HCP5 was revealed to function as a putative ceRNA of miR-138-5p to positively regulate EZH2, and EZH2 was shown to regulate autophagy and apoptosis of CSCC cells through the STAT3/VEGFR2 pathway. HCP5 overexpression decreased miR-138-5p levels, increased EZH2 levels and promoted cell malignant behaviors and autophagy but decreased the apoptosis rate. These trends were opposite when HCP5 was silenced. In conclusion, HCP5 may competitively bind to miR-138-5p to regulate EZH2 in CSCC cells, promoting autophagy and reducing apoptosis through the STAT3/VEGFR2 pathway. This study may provide a new perspective for understanding the molecular mechanism and treatment of CSCC.

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Section: Discussionmentioning

confidence: 99%

lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

2021

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“…Just as histone deacetylase inhibition is a potential target for cSCC therapy, so too is histone demethylase inhibition. Human cSCC cell lines were seen to have lysine demethylase (LSD1) inhibitor sensitivity, with the greatest sensitivity to a single‐molecule, dual‐action LSD1/HDAC inhibitor 116 …”

Section: Discussionmentioning

confidence: 99%

“…Human cSCC cell lines were seen to have lysine demethylase (LSD1) inhibitor sensitivity, with the greatest sensitivity to a single-molecule, dualaction LSD1/HDAC inhibitor. 116…”

Section: Histone Modification Enzymesmentioning

confidence: 99%

Molecular and immune targets in cutaneous squamous cell carcinoma

Galambus

Tsai

2022

Molecular Carcinogenesis

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Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and often confers a good prognosis. Though surgery is the gold standard of treatment, unresectable or metastatic disease can necessitate systemic therapy. Of systemic agents, there is increasing interest in the use of immunotherapies and targeted therapy. Further study into the driver mutations in cSCC has identified opportunities for targeted therapy. In this review, we discuss both current and investigational immune and molecular targets of therapy for cSCC.

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“…Effectively inhibiting the expression or function of LSD1 can mitigate the proliferation and dissemination of tumor cells, thereby markedly enhancing the therapeutic efficacy against cancer. Consequently, LSD1 has emerged as a compelling target for the development of anti-tumor drugs [ 27 , 28 ]. Despite LSD1 inhibitors’ extensive research, few have reached the market.…”

Section: Introductionmentioning

confidence: 99%

Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies

Han,

Lu,

Fan

et al. 2024

Molecules

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Lysine-specific demethylase 1 (LSD1/KDM1A) has emerged as a promising therapeutic target for treating various cancers (such as breast cancer, liver cancer, etc.) and other diseases (blood diseases, cardiovascular diseases, etc.), owing to its observed overexpression, thereby presenting significant opportunities in drug development. Since its discovery in 2004, extensive research has been conducted on LSD1 inhibitors, with notable contributions from computational approaches. This review systematically summarizes LSD1 inhibitors investigated through computer-aided drug design (CADD) technologies since 2010, showcasing a diverse range of chemical scaffolds, including phenelzine derivatives, tranylcypromine (abbreviated as TCP or 2-PCPA) derivatives, nitrogen-containing heterocyclic (pyridine, pyrimidine, azole, thieno[3,2-b]pyrrole, indole, quinoline and benzoxazole) derivatives, natural products (including sanguinarine, phenolic compounds and resveratrol derivatives, flavonoids and other natural products) and others (including thiourea compounds, Fenoldopam and Raloxifene, (4-cyanophenyl)glycine derivatives, propargylamine and benzohydrazide derivatives and inhibitors discovered through AI techniques). Computational techniques, such as virtual screening, molecular docking and 3D-QSAR models, have played a pivotal role in elucidating the interactions between these inhibitors and LSD1. Moreover, the integration of cutting-edge technologies such as artificial intelligence holds promise in facilitating the discovery of novel LSD1 inhibitors. The comprehensive insights presented in this review aim to provide valuable information for advancing further research on LSD1 inhibitors.

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LSD1: a viable therapeutic target in cutaneous squamous cell carcinoma?

Cited by 8 publications

References 72 publications

lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

lncRNA HCP5 acts as a ceRNA to regulate EZH2 by sponging miR‑138‑5p in cutaneous squamous cell carcinoma

Molecular and immune targets in cutaneous squamous cell carcinoma

Lysine-Specific Demethylase 1 Inhibitors: A Comprehensive Review Utilizing Computer-Aided Drug Design Technologies

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