Histone demethylase KDM7A controls androgen receptor activity and tumor growth in prostate cancer

Lee, Kyoung Hwa; Hong, Seokbong; Kang, Minyong; Jeong, Chang Wook; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

doi:10.1002/ijc.31843

Cited by 42 publications

(35 citation statements)

References 42 publications

(43 reference statements)

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“…The androgen‐activated transcription factor AR has been widely investigated. The AR features that contribute to the progression of prostate cancer consist of AR amplification, mutations, variants and alterations of coregulators, all of which lead to AR hyperactivity . In addition to what we described above, posttranscriptional regulation is also an efficient method for gene regulation.…”

Section: Discussionmentioning

confidence: 94%

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

et al. 2020

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractThe androgen receptor (AR) pathway is critical for prostate cancer carcinogenesis and development; however, after 18-24 months of AR blocking therapy, patients invariably progress to castration-resistant prostate cancer (CRPC), which remains an urgent problem to be solved. Therefore, finding key molecules that interact with AR as novel strategies to treat prostate cancer and even CRPC is desperately needed. In the current study, we focused on the regulation of RNA-binding proteins (RBPs) associated with AR and determined that the mRNA and protein levels of AR were highly correlated with Musashi2 (MSI2) levels. MSI2 was upregulated in prostate cancer specimens and significantly correlated with advanced tumor grades. Downregulation of MSI2 in both androgen sensitive and insensitive prostate cancer cells inhibited tumor formation in vivo and decreased cell growth in vitro, which could be reversed by AR overexpression. Mechanistically, MSI2 directly bound to the 3′-untranslated region (UTR) of AR mRNA to increase its stability and, thus, enhanced its transcriptional activity. Our findings illustrate a previously unknown regulatory mechanism in prostate cancer cell proliferation regulated by the MSI2-AR axis and provide novel evidence towards a strategy against prostate cancer. K E Y W O R D Sandrogen receptor, mRNA stability, Musashi2, novel anti-androgen therapy, prostate cancer

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Section: Discussionmentioning

confidence: 94%

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

et al. 2020

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“…circRNA: circular RNA; NOD-SCID: nonobese diabetic-severe combined immunodeficiency. therapeutic target for prostate cancer drugs 39 . In BrCa, KDM7A was defined as a tumor promoter.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED: Hsa_circ_002178 Promotes the Growth and Migration of Breast Cancer Cells and Maintains Cancer Stem-like Cell Properties Through Regulating miR-1258/KDM7A Axis

Yang

Shi

et al. 2020

Cell Transplant

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Breast cancer (BrCa) is the most common malignancy in women. Accumulating evidence demonstrated that abnormal circRNA expression is associated with the occurrence and progression of tumors. We analyzed the GSE101123 data and found that the expression of hsa_circ_002178 (circ_002178) was significantly increased in BrCa tissues. However, the role and possible underlying mechanisms of circ_002178 in BrCa still remain unrevealed. In this investigation, the expression levels of circ_002178 in cancer tissues or BrCa cells were significantly upregulated compared with those in paracancer tissues or normal cells. High expression of circ_002178 was correlated with the low survival rate, clinical tumor size, lymph node metastasis, and tumor, nodes, and metastases grade. After microsphere culture, the expression of circ_002178 in SUM149PT and MDA-MB-231 cells was significantly increased. Further investigation exhibited that overexpression of circ_002178 contributed to the formation of microspheres, the elevated protein levels of stemness marker, and the increased activity of ALDH1 in SUM149PT cells. Besides, the overexpression of circ_002178 also significantly promoted the growth, invasion, and migration of BrCa cells. Correspondingly, the knockdown of circ_002178 showed the opposite result in MDA-MB-231 cells. Hsa_circ_002178 was further proved to downregulate the level of miR-1258 and reduce the inhibitory effect of miR-1258 on KDM7A, thus regulating the stem-like characteristics of BrCa cells and promoting the growth and migration of BrCa cells. Taken together, targeting the circ_002178/miR-1258/KDM7A axis may be a prospective strategy for the diagnosis and therapies of BrCa in the future.

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“…Studies of the other members of the KDM7 family in cancer have thus far been more limited, and have uncovered both diseasepromoting and disease-suppressive roles. In prostate cancer, KDM7A is upregulated in expression and plays a role in AR-dependent gene expression and cell proliferation 175 . However, KDM7A expression is also induced under nutrient deprivation, and its ectopic overexpression in HeLa cells inhibits xenograft growth and angiogenesis 176 .…”

Section: Kdm7mentioning

confidence: 99%

Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

McCann

Sobral

Self

et al. 2019

Expert Opinion on Therapeutic Targets

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Introduction: Epigenetic mechanisms of gene regulatory control play fundamental roles in developmental morphogenesis, and, as more recently appreciated, are heavily implicated in the onset and progression of neoplastic disease, including cancer. Many epigenetic mechanisms are therapeutically targetable, providing additional incentive for understanding of their contribution to cancer and other types of neoplasia.

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Histone demethylase KDM7A controls androgen receptor activity and tumor growth in prostate cancer

Cited by 42 publications

References 42 publications

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

RNA‐binding protein Musashi2 stabilizing androgen receptor drives prostate cancer progression

RETRACTED: Hsa_circ_002178 Promotes the Growth and Migration of Breast Cancer Cells and Maintains Cancer Stem-like Cell Properties Through Regulating miR-1258/KDM7A Axis

Biology and targeting of the Jumonji-domain histone demethylase family in childhood neoplasia: a preclinical overview

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