PMID- 33668040
OWN - NLM
STAT- MEDLINE
DCOM- 20210722
LR  - 20210722
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 13
IP  - 4
DP  - 2021 Feb 26
TI  - Methylation-dependent MCM6 repression induced by LINC00472 inhibits 
      triple-negative breast cancer metastasis by disturbing the MEK/ERK signaling 
      pathway.
PG  - 4962-4975
LID - 10.18632/aging.103568 [doi]
AB  - Long noncoding RNAs (lncRNAs) have been identified to be dysregulated in multiple 
      cancer types, which are speculated to be of vital significance in regulating 
      several hallmarks of cancer biology. Triple-negative breast cancer (TNBC) is 
      acknowledged as an aggressive subtype of breast cancer. In this study, we found 
      the lncRNA LINC00472 was poorly expressed in TNBC tissues and cells. 
      Overexpression of LINC00472 could inhibit the proliferation, invasion and 
      migration of MDA-MB-231 cells. On the contrary, minichromosome maintenance 
      complex component 6 (MCM6) was highly expressed in TNBC tissues and MDA-MB-231 
      cells due to suppressed methylation. LINC00472 induced site-specific DNA 
      methylation and reduced the MCM6 expression by recruiting DNA methyltransferases 
      into the MCM6 promoter. Since the restoration of MCM6 weakened the 
      tumor-suppressive effect of LINC00472 on MDA-MB-231 cells, LINC00472 potentially 
      acted as a tumor suppressor by inhibiting MCM6. In addition, in vivo experiments 
      further substantiated that overexpression of LINC00472 inhibited tumor growth and 
      metastasis to lungs by decreasing the expression of MCM6. Overall, the present 
      study demonstrated that LINC00472-mediated epigenetic silencing of MCM6 
      contributes to the prevention of tumorigenesis and metastasis in TNBC, providing 
      an exquisite therapeutic target for TNBC.
FAU - Shao, Guoli
AU  - Shao G
AD  - Special Medical Service Center, Zhujiang Hospital of Southern Medical University, 
      Guangzhou 510280, P. R. China.
FAU - Fan, Xulong
AU  - Fan X
AD  - Department Breast Surgery, Maternity and Children's Healthcare Hospital of 
      Foshan, Foshan 528000, P. R. China.
FAU - Zhang, Pusheng
AU  - Zhang P
AD  - Department General Surgery, Zhujiang Hospital of Southern Medical University, 
      Guangzhou 510280, P. R. China.
FAU - Liu, Xuewen
AU  - Liu X
AD  - Special Medical Service Center, Zhujiang Hospital of Southern Medical University, 
      Guangzhou 510280, P. R. China.
FAU - Huang, Lei
AU  - Huang L
AD  - Department General Surgery, Zhujiang Hospital of Southern Medical University, 
      Guangzhou 510280, P. R. China.
FAU - Ji, Shufeng
AU  - Ji S
AD  - Special Medical Service Center, Zhujiang Hospital of Southern Medical University, 
      Guangzhou 510280, P. R. China.
LA  - eng
PT  - Journal Article
DEP - 20210226
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (CONCR long non coding RNA, human)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 3.6.4.12 (MCM6 protein, human)
RN  - EC 3.6.4.12 (Minichromosome Maintenance Complex Component 6)
SB  - IM
MH  - Carcinogenesis
MH  - DNA Methylation
MH  - Female
MH  - Humans
MH  - *MAP Kinase Signaling System
MH  - Middle Aged
MH  - Minichromosome Maintenance Complex Component 6/*genetics/metabolism
MH  - Neoplasm Metastasis/*prevention & control
MH  - RNA, Long Noncoding/*genetics
MH  - Triple Negative Breast Neoplasms/*genetics
PMC - PMC7950301
OTO - NOTNLM
OT  - LINC00472
OT  - long non-coding RNA
OT  - metastasis
OT  - minichromosome maintenance complex component 6
OT  - riple-negative breast cancer
COIS- CONFLICTS OF INTEREST: These authors declare no conflicts of interest.
EDAT- 2021/03/06 06:00
MHDA- 2021/07/23 06:00
PMCR- 2021/02/28
CRDT- 2021/03/05 20:20
PHST- 2020/01/09 00:00 [received]
PHST- 2020/04/17 00:00 [accepted]
PHST- 2021/03/05 20:20 [entrez]
PHST- 2021/03/06 06:00 [pubmed]
PHST- 2021/07/23 06:00 [medline]
PHST- 2021/02/28 00:00 [pmc-release]
AID - 103568 [pii]
AID - 10.18632/aging.103568 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2021 Feb 26;13(4):4962-4975. doi: 10.18632/aging.103568. Epub 
      2021 Feb 26.