PMID- 38448424
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240309
IS  - 2058-7716 (Print)
IS  - 2058-7716 (Electronic)
IS  - 2058-7716 (Linking)
VI  - 10
IP  - 1
DP  - 2024 Mar 6
TI  - LSD1 modulates the bone metastasis of breast cancer cells through 
      hnRNPA2B1-mediated sorting of exosomal miRNAs.
PG  - 115
LID - 10.1038/s41420-024-01897-5 [doi]
LID - 115
AB  - Bone metastasis is a key contributor to morbidity and mortality of breast cancer 
      patients. We have previously shown that exosomal miRNAs derived from LSD1 
      knockdown (KD) breast cancer cells inhibit osteoblast differentiation and promote 
      osteoclast differentiation. However, how LSD1 regulates exosomal miRNAs and 
      whether miRNAs promote bone metastasis through the formation of pre-metastatic 
      niches remains unclear. In vivo experiments demonstrates that exosomes derived 
      from LSD1 KD breast cancer cells significantly promoted bone metastasis. To 
      explore the mechanism underlying the effect of LSD1 on exosomes in breast cancer 
      cells, exosomal and cellular miRNAs from control, LSD1 KD, and rescue cells were 
      sequenced. Interestingly, approximately 80% of LSD1-associated miRNAs were 
      downregulated in exosomes from LSD1 KD cells. The consensus sequence UAGGGC, was 
      identified in many miRNAs downregulated in LSD1 KD exosomes. We found that 
      hnRNPA2B1 regulated the exosomal sorting of miR-6881-3p and some other miRNAs. 
      LSD1 deficiency reduced hnRNPA2B1 expression in breast cancer cells by decreasing 
      the level of H3K9me2 demethylation in the promoter region of the hnRNPA2B1 gene. 
      Our study revealed that LSD1 plays a crucial role in the regulation of exosomal 
      sorting of miRNA.
CI  - (c) 2024. The Author(s).
FAU - Liu, Ziyu
AU  - Liu Z
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
AD  - School of Life Sciences, Jilin University, Changchun, Jilin, 130012, China.
FAU - Xin, Benkai
AU  - Xin B
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - Zhang, Nan
AU  - Zhang N
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - An, Peipei
AU  - An P
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - Shi, Yueru
AU  - Shi Y
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - Yang, Jingtong
AU  - Yang J
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - Wan, Youzhong
AU  - Wan Y
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - He, Yuquan
AU  - He Y
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China.
FAU - Hu, Xin
AU  - Hu X
AUID- ORCID: 0000-0002-5105-8929
AD  - China-Japan Union Hospital of Jilin University, Jilin University, Changchun, 
      Jilin, 130033, China. huxin@jlu.edu.cn.
LA  - eng
GR  - 20230508066RC/Department of Science and Technology of Jilin Province (Jilin 
      Province Science and Technology Department)/
GR  - 2022scz04/Department of Finance of Jilin Province (Jilin Provincial Department of 
      Finance)/
PT  - Journal Article
DEP - 20240306
PL  - United States
TA  - Cell Death Discov
JT  - Cell death discovery
JID - 101665035
PMC - PMC10917739
COIS- The authors declare no competing interests.
EDAT- 2024/03/07 00:42
MHDA- 2024/03/07 00:43
PMCR- 2024/03/06
CRDT- 2024/03/06 23:15
PHST- 2023/12/15 00:00 [received]
PHST- 2024/02/27 00:00 [accepted]
PHST- 2024/02/22 00:00 [revised]
PHST- 2024/03/07 00:43 [medline]
PHST- 2024/03/07 00:42 [pubmed]
PHST- 2024/03/06 23:15 [entrez]
PHST- 2024/03/06 00:00 [pmc-release]
AID - 10.1038/s41420-024-01897-5 [pii]
AID - 1897 [pii]
AID - 10.1038/s41420-024-01897-5 [doi]
PST - epublish
SO  - Cell Death Discov. 2024 Mar 6;10(1):115. doi: 10.1038/s41420-024-01897-5.