Expanding the Role of the Histone Lysine-Specific Demethylase LSD1 in Cancer

Majello, Barbara; Gorini, Francesca; Saccà, Carmen D.; Amente, Stefano

doi:10.3390/cancers11030324

Cited by 112 publications

(103 citation statements)

References 93 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Lysine‐Specific histone Demethylases LSD1 and LSD2 are two homologous enzymes that demethylate H3K4me1 and H3K4me2. [ 81 ] LSD1 associates with CoREST or NuRD complex that leads to gene repression, whereas LSD2 in association with the cytokine‐like nuclear factor NPAC is involved in transcriptional elongation. [ 82 ] A linker peptide of NPAC stimulates LSD2 activity.…”

Section: Ptms In Complex With Nucleosomementioning

confidence: 99%

Structural Basis of Nucleosome Recognition and Modulation

Sundaram

Vasudevan

2020

BioEssays

View full text Add to dashboard Cite

Chromatin structure and dynamics regulate key cellular processes such as DNA replication, transcription, repair, remodeling, and gene expression, wherein different protein factors interact with the nucleosomes. In these events, DNA and RNA polymerases, chromatin remodeling enzymes and transcription factors interact with nucleosomes, either in a DNA‐sequence‐specific manner and/or by recognizing different structural features on the nucleosome. The molecular details of the recognition of a nucleosome by different viral proteins, remodeling enzymes, histone post‐translational modifiers, and RNA polymerase II, have been explored in the recent past. The present review puts forth critical insights into the basic mechanisms of nucleosome recognition by the various protein factors and the role of distinct surface epitopes on a nucleosome. These determinants of the underlying specificity include features such as the acidic patch, arginine anchor, histone post‐translational modifications, core DNA, DNA lesions, and linker DNA.

show abstract

Section: Ptms In Complex With Nucleosomementioning

confidence: 99%

Structural Basis of Nucleosome Recognition and Modulation

Sundaram

Vasudevan

2020

BioEssays

View full text Add to dashboard Cite

show abstract

“…For the 23 patients who acquired 5-FU resistance, 19 cases (82.6%) exhibited strong, 3 cases (13%) moderate, and 1 case (4.4%) weak immunopositivity ( Figure 1E). Conversely, for the 37 exhibited weak or no immunopositivity ( Figure 1E), These results indicated that LSD1 upregulation in CRC tissues is associated with 5-FU resistance in patients. Taken together, our results suggest that LSD1 overexpression is tightly linked to CRC development and 5-FU resistance.…”

Section: Lsd1 Overexpression In Human Crc Tissues Is Correlated With mentioning

confidence: 75%

Synergistic antitumor effect of 5-fluorouracil with the novel LSD1 inhibitor ZY0511 in colorectal cancer

et al. 2020

View full text Add to dashboard Cite

Background: Lysine-specific histone demethylase 1 (LSD1) is a potential target of cancer therapy. In the present study, we aimed to investigate the combined antitumor activity of a novel LSD1 inhibitor (ZY0511) with 5-fluorouracil (5-FU) and elucidate the underlying mechanism in colorectal cancer (CRC). Methods: We evaluated LSD1 expression in CRC tissues from patients who received 5-FU treatment. The synergistic antitumor effect of 5-FU with ZY0511 against human CRC cells was detected both in vitro and in vivo. The underlying mechanism was explored based on mRNA sequencing (mRNA-seq) technology. Results: Overexpression of LSD1 was observed in human CRC tissues, and correlated with CRC development and 5-FU resistance. ZY0511, a novel LSD1 inhibitor, effectively inhibited CRC cells proliferation, both in vitro and in vivo. Notably, the combination of ZY0511 and 5-FU synergistically reduced CRC cells viability and migration in vitro. It also suppressed Wnt/β-catenin signaling and DNA synthesis pathways, which finally induced apoptosis of CRC cells. In addition, the combination of ZY0511 with 5-FU significantly reduced CRC xenograft tumor growth, along with lung and liver metastases in vivo. Conclusions: Our findings identify LSD1 as a potential marker for 5-FU resistance in CRC. ZY0511 is a promising candidate for CRC therapy as it potentiates 5-FU anticancer effects, thereby providing a new combinatorial strategy for treating CRC.

show abstract

“…Furthermore, it was also found that LSD1 expression markedly enhanced in GC tissues relative to the normal tissues, and LSD1 knockdown obviously impaired the proliferation and migration of GC cells. LSD1 is a member of the flavin-dependent LSD/KDM1 demethylase protein family, and is reported as a transcription repressor that can demethylate H3K4me1/me2 [29][30][31][32] . To explore the related signals and underlying targets that participate in the regulation of LINC01446-LSD1 axis in GC on an unbiased basis, we conducted high-throughput RNA sequencing following the knockdown of LINC01446 in SGC7901 cells.…”

Section: Discussionmentioning

confidence: 99%

Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1

et al. 2020

View full text Add to dashboard Cite

Growing evidences illustrated that long non-coding RNAs (lncRNAs) exhibited widespread effects on the progression of human cancers via various mechanisms. Long intergenic non-protein-coding RNA 01446 (LINC01446), a 3484-bp ncRNA, is known to locate at chromosome 7p12.1. However, its biological functions and specific action mechanism in gastric cancer (GC) are still unclear. In our study, LINC01446 was proved to be markedly upregulated in GC tissues relative to the normal tissues, and positively correlated with the poor survival of GC patients. The multivariate Cox regression model showed that LINC01446 functioned as an independent prognostic factor for the survival of GC patients. Functionally, LINC01446 facilitated the proliferation and metastasis of GC cells. Moreover, RNA-seq analysis demonstrated that LINC01446 knockdown primarily regulated the genes relating to the growth and migration of GC. Mechanistically, LINC01446 could widely interact with histone lysine-specific demethylase LSD1 and recruit LSD1 to the Ras-related dexamethasone-induced 1 (RASD1) promoter, thereby suppressing RASD1 transcription. Overall, these findings suggest that LINC01446/LSD1/RASD1 regulatory axis may provide bona fide targets for anti-GC therapies.

show abstract

Expanding the Role of the Histone Lysine-Specific Demethylase LSD1 in Cancer

Cited by 112 publications

References 93 publications

Structural Basis of Nucleosome Recognition and Modulation

Structural Basis of Nucleosome Recognition and Modulation

Synergistic antitumor effect of 5-fluorouracil with the novel LSD1 inhibitor ZY0511 in colorectal cancer

Long intergenic non-protein-coding RNA 01446 facilitates the proliferation and metastasis of gastric cancer cells through interacting with the histone lysine-specific demethylase LSD1

Contact Info

Product

Resources

About