Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma

Cao, Linlin; Du, Changsheng; Liu, Hangqi; Pei, Lirong; Li, Qin; Jia, Ming; Wang, Hui

doi:10.1177/1724600818764069

Cited by 11 publications

(9 citation statements)

References 29 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The flavin-dependent KDM family includes LSD1 (KDM1A/AOF2) and LSD2 (KDM1B/AOF1) [ 12 ]. LSD1 has been shown to be overexpressed in colorectal cancer and to promote the growth and invasion of colorectal cancer [ 16 , 17 ]. Although the function of LSD2 in the biology of other cancers such as breast cancer has been described in detail [ 15 ], the expression and function of LSD2 in CRC has not been reported until now.…”

Section: Discussionmentioning

confidence: 99%

“…Although the effect of p53 on the role of the LSD family in colorectal cancer has been studied before, it remains controversial. Although it has been reported that LSD1 can regulate p53 by removing both monomethoxylation (k370me1) and dimerization (k370me2) at k370 [ 30 ], it has been reported that the expression of p53 is not related to LSD1 in CRC tissue [ 17 ].In our study, p53 was correlated with LSD2 function in CRC. We showed that LSD2 overexpression downregulated the protein levels of p53, while LSD2 knockdown upregulated p53.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, LSD2 overexpression predicts aggressive tumor biology and poor prognosis [ 15 ]. However, while high LSD1 expression has been found in CRC tissues [ 16 ], which promotes the proliferation and colony formation of CRC cells [ 17 ], the role of LSD2 in CRC biology remains largely unknown.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

Cai

Wang

Zeng

et al. 2020

Aging

View full text Add to dashboard Cite

Epigenetic alterations have been reported to play critical roles in the development of colorectal cancer (CRC). However, the biological function of the lysine-specific histone demethylase 1B (LSD2/KDM1B) in CRC is not well understood. Therefore, we investigated the characteristics of LSD2 in CRC. We observed significant upregulation of LSD2 in CRC tissue compared to that in normal colorectal tissue. LSD2 promotes CRC cell proliferation and inhibits cell apoptosis through cell cycle regulation, promoting CRC progression both in vitro and in vivo. We found that LSD2 performs these functions by inhibiting the p53-p21-Rb pathway. Finally, we found that LSD2 directly binds to p53 and represses p53 expression via H3K4me2 demethylation at the p53 promoter. Our results revealed that LSD2 acts as an oncogene by binding and inhibiting p53 activity in CRC. Thus, LSD2 may be a new molecular target for CRC treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

Cai

Wang

Zeng

et al. 2020

Aging

View full text Add to dashboard Cite

show abstract

“…KDM2A was first discovered in kidney COS-7 cells exhibiting robust histone demethylase activity (10). KDM2A was found to be highly expressed in lung (11), pancreatic cancer (12), colorectal adenocarcinoma (13), breast (14), gastric cancer (15) and certain blood diseases (16), which have been reported to be related to tumor aggressiveness and metastasis, chemotherapy resistance and poor prognosis. This protein has been linked to many signaling pathways, which promote cancer metastasis and malignancy.…”

Section: Introductionmentioning

confidence: 99%

Lysine demethylase�2A promotes the progression of ovarian cancer by regulating the PI3K pathway and reversing epithelial‑mesenchymal transition

Yang

Gao

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Metastasis is the most common cause of death in ovarian cancer patients but remains largely untreated. Epithelial-mesenchymal transition (EMT) is critical for the conversion of early-stage ovarian tumors into metastatic malignancies. Thus, investigating the signaling pathways promoting EMT may identify potential targets for the treatment of metastatic ovarian cancer. Lysine demethylase 2A (KDM2A), also known as FBXL11 and JHDM1A, is a histone H3 lysine 36 (H3K36) demethylase that regulates EMT and the metastasis of ovarian cancer. However, the function and underlying mechanisms of EMT suppression in ovarian cancer have not been thoroughly elucidated to date. In the present study, we used Gene Expression Omnibus (GEO) databases to determine that KDM2A is significantly upregulated in human ovarian cancers. KDM2A expression was assessed by immunohistochemistry of epithelial ovarian cancer (EOC) borderline ovarian tumors and normal ovary tissues. Seven fresh EOC tissues and 3 fresh normal ovary tissues were collected for western blot analysis. Kaplan-Meier survival curves were constructed to identify genes related to EOC prognosis from the TCGA data portal. Stable KDM2A-knockdown cell lines were established to study the biological functions and underlying mechanisms of KDM2A in EMT in vitro. GEO database analysis revealed that KDM2A was highly upregulated in EOC tissues; this analysis was accompanied by immunochemistry and western blot analysis using samples of human tissues. High expression of KDM2A was associated with poor survival in EOC patients. KDM2A knockdown promoted apoptosis and suppressed the proliferation, migration and invasion of tumor cells in vitro. EMT and the PI3K/AKT/mTOR signaling pathway were suppressed in KDM2A-silenced cells. Inactivation of the PI3K/AKT/mTOR signaling pathway in A2780 cells induced EMT inhibition. Our data revealed that KDM2A functions as a tumor oncogene, and the downregulation of KDM2A expression regulates EMT and EOC progression, providing a valuable prognostic marker and potential target for the treatment of EOC patients.

show abstract

“…LSD2 has been noted to be overexpressed in several malignancies such as colorectal adenocarcinoma, small cell lung cancer and breast cancer [16, 17, 18]. Recent studies with breast cancer cell lines showed that overexpression of LSD2 led to increased cell proliferation and oncogenic transformation, but decreased cellular motility and invasion [15].…”

Section: Introductionmentioning

confidence: 99%

Investigating the role of LSD2 as an epigenetic regulator in Ewing sarcoma

et al. 2019

View full text Add to dashboard Cite

Ewing sarcoma is the second most common solid bone malignancy diagnosed in pediatric and young adolescent populations. Despite aggressive multi-modal treatment strategies, 5-year event-free survival remains at 75% for patients with localized disease and 20% for patients with metastases. Thus, the need for novel therapeutic options is imperative. Recent studies have focused on epigenetic misregulation in Ewing sarcoma development and potential new oncotargets for treatment. This project focused on the study of LSD2, a flavin-dependent histone demethylase found to be overexpressed in numerous cancers. We previously demonstrated that Ewing sarcoma cell lines are extremely susceptible to small molecule LSD1 blockade with SP-2509. Drug sensitivity correlated with the degree of LSD2 induction following treatment. As such, the purpose of this study was to determine the role of LSD2 in the epigenetic regulation of Ewing sarcoma, characterize genes regulated by LSD2, and examine the impact of SP-2509 drug treatment on LSD2 gene regulation. Genetic depletion (shRNA) of LSD2 significantly impaired oncogenic transformation with only a modest impact on proliferation. Transcriptional analysis of Ewing sarcoma cells following LSD2knockdown revealed modulation of genes primarily involved in metabolic regulation and nervous system development. Gene set enrichment analysis showed that SP-2509 does not impact LSD2 targeted genes. Although there are currently no small molecule agents that specifically target LSD2, our results support further investigations into agents that can inhibit this histone demethylase as a possible treatment for Ewing sarcoma.

show abstract

Lysine-specific demethylase 2A expression is associated with cell growth and cyclin D1 expression in colorectal adenocarcinoma

Abstract: Our study reveals a novel role for high-expressed KDM2A in colorectal adenocarcinoma cell growth, and that the expression of KDM2A is associated with that of cyclin D1 in colorectal adenocarcinoma.

Cited by 11 publications

References 29 publications

Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

Lysine-specific histone demethylase 1B (LSD2/KDM1B) represses p53 expression to promote proliferation and inhibit apoptosis in colorectal cancer through LSD2-mediated H3K4me2 demethylation

Lysine demethylase�2A promotes the progression of ovarian cancer by regulating the PI3K pathway and reversing epithelial‑mesenchymal transition

Investigating the role of LSD2 as an epigenetic regulator in Ewing sarcoma

Contact Info

Product

Resources

About