KDM1A overexpression

In conclusion, our study provides compelling evidence that apigenin inhibits liver cancer progression and elucidates its mechanism of action in regulating lipid metabolism. Specifically, we find that apigenin suppresses the progression of HCC cells by downregulating genes involved in lipid metabolism. Additionally, our results indicate that KDM1A acts as a downstream target of apigenin in the inhibition of lipid metabolism in HCC. These findings offer experimental support for the potential use of apigenin as a therapeutic agent for liver cancer, highlighting its relevance in future clinical applications.

In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.

In this work, we designed PCPA-entinostat conjugates for selective cancer cell targeting. PCPA-entinostat conjugate 12 with a 4-oxybenzyl group linker released entinostat in the presence of LSD1 in in vitro assays and selectively inhibited the growth of cancer cells in preference to normal cells, suggesting the potential of PCPA-entinostat conjugates as novel anticancer drug delivery small molecules.

LSD1 was shown to participate in an intriguing antiviral mechanism, where it activates endolysosomal interferon-induced transmembrane protein 3 (IFITM3) via demethylation, leading endocytosed HCV virions to degradation. Our study proposes that HCV-mediated LSD1 oscillations over countless viral life cycles throughout chronic HCV infection may promote epigenetic changes related to HCV-induced hepatocarcinogenesis.

The primary endpoint is ORR per RECIST 1.1; secondary endpoints include rate of ≥ grade 3 toxicities, PFS, OS and DoR. Exploratory endpoints include host inflammatory cytokine and immune profile, and epigenomic and genomic analysis of tumor and peripheral blood samples.

Lastly, loss of KDM1A markedly reduced 53BP1 DNA repair foci, implying the involvement of KDM1A in the DNA damage response. Overall, our results indicate that KDM1A impacts CRC progression in several non-overlapping ways, and therefore it represents a promising epigenetic target to prevent tumor relapse.

Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.

In this study, we screened an in-house small-molecule library targeting LSD1, an FDA-approved drug amsacrine for acute leukemia and malignant lymphomas was found to exhibit moderate anti-LSD1 inhibitory activity (IC = 0.88 μM)...Moreover, tumor growth was also suppressed by compound 6x in mice. Altogether, our findings demonstrated that acridine-based novel LSD1 inhibitor 6x may be a lead compound for the development of activating T cell immune response in gastric cancer cells.

In conclusion, YTHDF2 promotes breast cancer cell growth and cell cycle progression by facilitating KDM1A mRNA stability. This study provides new therapeutic targets for breast cancer treatment in the future.

Our results provide compelling evidence KDM1A is essential for DNA repair in GSCs and KDM1A inhibition sensitizes GBM to TMZ via attenuation of DNA repair pathways. These findings suggest combination therapy of KDM1A inhibitor NCD38 with TMZ is a potential novel therapeutic strategy to improve GBM outcomes.

In this review, we compiled what is known about the LSD1 function in various sarcomas, to determine where knowledge is lacking and to find what theme emerge to characterize how LSD1 is a key molecular driver in bone and soft tissue sarcoma. We further discuss the current clinical landscape for the development of LSD1 inhibitors and where sarcomas have been included in early clinical trials.

These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.

Collectively, our study revealed that salinomycin suppressed T24 cell proliferation and promoted oxidative stress and apoptosis by regulating KDM1A and the UPR pathway. The online version contains supplementary material available at 10.1007/s10616-022-00546-y.

KDM1A is a regulator of cellular UV response, and KDM1A inhibition can improve PDT efficacy.

We demonstrated that LSD1 is overexpressed in RB cells and promotes RB cell survival. The LSD1 inhibitor SP2509 exerted strong growth inhibition in vitro and in vivo, which was at least partially mediated by suppression of the β-catenin pathway.

Here, we unraveled a novel mode of action of the LSD1 inhibitors MC2580 and DDP-38003, showing that they can induce differentiation of AML cells through the downregulation of the chromatin protein GSE1...Moreover, we show that LSD1 inhibitors lead to the reduced binding of GSE1 to these promoters, activating transcriptional programs that trigger myeloid differentiation. Our study offers new insights into GSE1 as a novel therapeutic target for AML.

Collectively, our results provide compelling evidence that KDM1A inhibition potentiates the activity of mTOR inhibitors by attenuating the feedback activation of Akt survival signaling. Furthermore, the use of concurrent KDM1A and mTOR inhibitors may be an attractive targeted therapy for EC patients.

Moreover, the alterations caused by OTUB2 overexpression were partly inversed by KDM1A knockdown and in turn KDM1A overexpression reversed the changes induced by OTUB2 shRNA. Taken together, we demonstrate that OTUB2 may serve as a vital driver in GC tumorigenesis by enhancing KDM1A-mediated stem cell-like properties.

In vivo xenograft experiments confirmed that intraperitoneal administration of ZY0511 significantly suppressed SU-DHL-6 xenograft tumor growth in vivo. In conclusion, our findings identify that ZY0511 inhibits DLBCL growth both in vitro and in vivo via the induction of apoptosis and autophagy, and LSD1 inhibitor might be a promising strategy for treating DLBCL.

Furthermore, in MGC-803 xenograft mouse model, 5k treatment resulted in significant reduction in tumor size by 81.6% and 96.1% at dosages of 40 and 80 mg/kg/d, respectively. Our findings indicate that erlotinib-based analogs provide a novel structural set of LSD1 inhibitors with potential for further investigation, and may serve as novel candidates for the treatment of LSD1-overexpressing cancers.

Cotransfection of KDM1A and DACT1 overexpression could reverse the increased cell proliferation and migration ability induced by KDM1A overexpression. KDM1A can downregulate DACT1 expression through histone deacetylation and therefore suppress the proliferation and migration of cervical cancer cells.