PMID- 35014621
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20240204
IS  - 0219-1032 (Electronic)
IS  - 1016-8478 (Print)
IS  - 1016-8478 (Linking)
VI  - 45
IP  - 4
DP  - 2022 Apr 30
TI  - Menin Enhances Androgen Receptor-Independent Proliferation and Migration of 
      Prostate Cancer Cells.
PG  - 202-215
LID - 10.14348/molcells.2021.0206 [doi]
AB  - The androgen receptor (AR) is an important therapeutic target for treating 
      prostate cancer (PCa). Moreover, there is an increasing need for understanding 
      the AR-independent progression of tumor cells such as neuroendocrine 
      prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia 
      type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia 
      (MLL) complex in PCa development by activating AR target genes through histone H3 
      lysine 4 methylation. Although menin is a critical component of AR signaling, its 
      tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared 
      the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or 
      pharmacological inhibition of menin. We demonstrated that menin was involved in 
      tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. 
      The inhibition of menin significantly diminished the growth of PCa cells and 
      induced apoptosis, regardless of the presence of AR. Additionally, transcriptome 
      analysis showed that the expression of many metastasis-associated genes was 
      perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, 
      wound-healing assay results showed that menin promoted cell migration in 
      AR-independent cellular contexts. Overall, these findings suggest a critical 
      function of menin in tumorigenesis and provide a rationale for drug development 
      against menin toward targeting high-risk metastatic PCa, especially those 
      independent of AR.
FAU - Kim, Taewan
AU  - Kim T
AUID- ORCID: 0000-0003-2770-2849
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
AD  - These authors contributed equally to this work.
FAU - Jeong, Kwanyoung
AU  - Jeong K
AUID- ORCID: 0000-0002-8415-7480
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
AD  - These authors contributed equally to this work.
FAU - Kim, Eunji
AU  - Kim E
AUID- ORCID: 0000-0002-6120-6390
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
FAU - Yoon, Kwanghyun
AU  - Yoon K
AUID- ORCID: 0000-0002-3746-5237
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
FAU - Choi, Jinmi
AU  - Choi J
AUID- ORCID: 0000-0002-4909-9473
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
FAU - Park, Jae Hyeon
AU  - Park JH
AUID- ORCID: 0000-0002-8463-6086
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
FAU - Kim, Jae-Hwan
AU  - Kim JH
AUID- ORCID: 0000-0002-1347-9909
AD  - NineBiopharm, Co., Ltd., Cheongju 28161, Korea.
AD  - National Creative Research Center for Epigenome Reprogramming Network, Department 
      of Biomedical Sciences, Seoul National University College of Medicine, Seoul 
      03080, Korea.
FAU - Kim, Hyung Sik
AU  - Kim HS
AUID- ORCID: 0000-0001-7657-3970
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
FAU - Youn, Hong-Duk
AU  - Youn HD
AUID- ORCID: 0000-0001-9741-8566
AD  - National Creative Research Center for Epigenome Reprogramming Network, Department 
      of Biomedical Sciences, Seoul National University College of Medicine, Seoul 
      03080, Korea.
FAU - Cho, Eun-Jung
AU  - Cho EJ
AUID- ORCID: 0000-0002-6610-5329
AD  - School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Cells
JT  - Molecules and cells
JID - 9610936
RN  - 0 (Receptors, Androgen)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Humans
MH  - Male
MH  - *Prostatic Neoplasms/genetics/metabolism
MH  - *Receptors, Androgen/genetics/metabolism
MH  - Signal Transduction
MH  - Transcription Factors
PMC - PMC9001152
OTO - NOTNLM
OT  - androgen receptor
OT  - menin
OT  - menin inhibitor
OT  - metastasis
OT  - prostate cancer
COIS- CONFLICT OF INTEREST The authors have no potential conflicts of interest to 
      disclose.
EDAT- 2022/01/12 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/01/03
CRDT- 2022/01/11 08:44
PHST- 2021/08/03 00:00 [received]
PHST- 2021/11/19 00:00 [revised]
PHST- 2021/12/07 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/01/11 08:44 [entrez]
PHST- 2022/01/03 00:00 [pmc-release]
AID - S1016-8478(23)00092-4 [pii]
AID - molce-45-4-202 [pii]
AID - 10.14348/molcells.2021.0206 [doi]
PST - ppublish
SO  - Mol Cells. 2022 Apr 30;45(4):202-215. doi: 10.14348/molcells.2021.0206.