JMJD2C triggers the growth of multiple myeloma cells via activation of β‑catenin

Abstract

Emerging evidence has indicated that histone modification and its related regulators are involved in the progression of multiple myeloma (MM) cells. In the present study, the expression of Jumonji C domain-containing 2 (JMJD2) was examined in both MM tissues and healthy controls. The roles of JMJD2C in the progression of MM were further investigated. The results revealed that the expression of JMJD2C, but not that of JMJD2A or JMJD2B, was increased in MM tissues compared with the healthy controls. The overexpression of JMJD2C significantly increased the in vitro growth of MM cells. The inhibitor of the β-catenin signaling pathway significantly attenuated the JMJD2C-induced growth of MM cells. Mechanistical analyses indicated that JMJD2C increased the transcription of β-catenin in MM cells, which may be due to the fact that JMJD2C can directly bind with the promoter of β-catenin. Furthermore, JMJD2C activated β-catenin in MM cells via a GSK3β-dependent manner, which was evidenced by the results demonstrating that the overexpression of GSK3β attenuated the JMJD2C-induced decrease in the phosphorylation of β-catenin. On the whole, the findings of the present study demonstrated that JMJD2C promotes the malignancy of MM via the activation of the β-catenin pathway. These results suggested that JMJD2C may be a potential target for MM treatment.

KDM4C Promotes Proliferation and Migration of Multiple Myeloma Cells by Up-Regulating JAG1 Gene Expression

“…Results showed that KDM4C was elevated in the plasma of multiple myeloma patients and multiple myeloma cells. These results was consistent with the previous study 9) . Lv et al, revealed that KDM4C was elevated in bone marrow samples of multiple myeloma patients 9) .…”

“…These results was consistent with the previous study 9) . Lv et al, revealed that KDM4C was elevated in bone marrow samples of multiple myeloma patients 9) . The high expression of KDM4C is also found in other cancers such as prostate cancer, ovarian cancer, colon cancer, non-small cell lung cancer (NSCLC), and glioblastoma 6-8, 19, 20) .…”

“…Besides, KDM4C was elevated in bone marrow samples of multiple myeloma patients 9) . However, the role of KDM4C in multiple myeloma remains elusive currently.…”

Pathobiology and Therapeutic Relevance of GSK-3 in Chronic Hematological Malignancies

“…There is a study which demonstrates how GSK-3 potentially has tumor-suppressive functions in MM; however, its activity is restrained by Akt activation, thereby resulting in the stabilization of Mcl-1 levels [ 157 ]. Another restrainer of GSK-3 in MM cells is the histone demethylase KDM4C, which is upregulated in MM patients and, when overexpressed in MM cell lines, increases β-catenin levels and activity while decreasing both the RNA and protein expression of GSK-3β [ 158 ]. Finally, there is evidence that lenalidomide (a drug widely used for treating MM patients [ 159 ]) induces activation of Wnt/β-catenin signaling.…”

Transcriptomic and Drug Discovery Analyses Reveal Natural Compounds Targeting the KDM4 Subfamily as Promising Adjuvant Treatments in Cancer

“…KDM4B promotes carcinogenesis in estrogen receptor-positive breast cancer ( Yang et al, 2010 ; Kawazu et al, 2011 ) and has also been associated with poor outcomes in gastric cancer ( Wu et al, 2019 ), castration-resistant prostate cancer ( Sha et al, 2020 ) and osteosarcoma ( Liu et al, 2020 ). KDM4C promotes malignancy in multiple neoplasms, such as multiple myeloma ( Lv and Liu, 2021 ), glioblastoma ( Lee et al, 2021 ), and squamous cell carcinoma ( Labbé et al, 2013 ).…”