MALAT1 regulates the transcriptional and translational levels of proto-oncogene RUNX2 in colorectal cancer metastasis.
Biomarkers
/ metabolism
Colorectal Neoplasms
/ genetics
Core Binding Factor Alpha 1 Subunit
/ genetics
Gene Knockout Techniques
Humans
MicroRNAs
/ metabolism
Neoplasm Metastasis
/ genetics
Nerve Tissue Proteins
/ metabolism
Polypyrimidine Tract-Binding Protein
/ metabolism
Protein Biosynthesis
Proto-Oncogene Mas
RNA, Long Noncoding
/ metabolism
Recurrence
Signal Transduction
Survival Analysis
Transcription, Genetic
beta Catenin
/ metabolism
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
16 05 2019
16 05 2019
Historique:
received:
20
11
2018
accepted:
12
04
2019
revised:
12
04
2019
entrez:
18
5
2019
pubmed:
18
5
2019
medline:
26
6
2020
Statut:
epublish
Résumé
Ectopic expression of lncRNA-MALAT1 has been discovered in recurrent colorectal cancer (CRC) and metastatic sites in postsurgical patients, however, its biological mechanism remained unelucidated. Our study first revealed the novel roles of MALAT1 in promoting CRC metastasis through two mechanisms: first, MALAT1 binds miR-15 family members, to "de-inhibit" their effect on LRP6 expression, enhances β-catenin signaling, leading to elevated transcriptional levels of downstream target genes RUNX2. Second, MALAT1 binds SFPQ, and dissociates SFPQ/PTBP2 dimer to release free PTBP2, which elevates translational levels of RUNX2, through interacting with IRES domain in the 5'UTR of the corresponding RUNX2 mRNAs. Moreover, increased RUNX2 expression levels were detected in recurrent CRC tumors, which were closely associated with TMN stages, metastasis, as well as CRC patients' survival. Our study demonstrated that MALAT1 and RUNX2 may serve as two biomarkers for predicting the recurrence and metastasis of CRC patients.
Identifiants
pubmed: 31097689
doi: 10.1038/s41419-019-1598-x
pii: 10.1038/s41419-019-1598-x
pmc: PMC6522477
doi:
Substances chimiques
Biomarkers
0
Core Binding Factor Alpha 1 Subunit
0
MALAT1 long non-coding RNA, human
0
MAS1 protein, human
0
MIRN15 microRNA, human
0
MicroRNAs
0
Nerve Tissue Proteins
0
PTBP2 protein, human
0
Proto-Oncogene Mas
0
RNA, Long Noncoding
0
RUNX2 protein, human
0
beta Catenin
0
Polypyrimidine Tract-Binding Protein
139076-35-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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