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MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer
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MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer
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Journal Article
MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer
2023
Overview
Background
The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (
MALAT1
) is a cancer biomarker. Furthermore, fusion of the
MALAT1
gene with glioma-associated oncogene 1 (
GLI1
) is a diagnostic marker of plexiform fibromyxoma and gastroblastoma; however, the function of this fusion gene remains unexplored.
Method
In this study, we elucidate the structure and function of the
MALAT1::GLI1
fusion gene. To this end, we determined a transcriptional start site (TSS) and promoter region for truncated GLI1 expression using rapid amplification of the 5' cDNA end and a luciferase reporter assay in cultured cells transfected with a plasmid harboring the
MALAT1::GLI1
fusion gene.
Results
We found that the TATA box, ETS1 motif, and TSS were located in
MALAT1
and that
MALAT1
exhibited transcriptional activity and induced expression of
GLI1
from the
MALAT1::GLI1
fusion gene. Truncated GLI1, lacking SUMOylation and SUFU binding sites and located in the nucleus, upregulated mRNA expression of GLI1 target genes in the hedgehog signaling pathway.
Conclusions
We demonstrate a distinct and alternative function of
MALAT1
as a transcriptional promoter for expression of the
MALAT1::GLI1
fusion gene. Our findings will aid future research on
MALAT1
and its fusion gene partners.
Publisher
Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Biomedical and Life Sciences
/ Cancer
/ Cloning
/ GLI1
/ Glioma
/ Health Promotion and Disease Prevention
/ Hedgehog Proteins - genetics
/ Humans
/ Kinases
/ MALAT1
/ Mutation
/ Neoplasms. Tumors. Oncology. Including cancer and carcinogens
/ Oncology
/ Plasmids
/ Proteins
/ RNA, Long Noncoding - genetics
/ RNA, Long Noncoding - metabolism
/ Stomach Neoplasms - pathology
/ Structure-function relationships
/ Tata box
/ Transcription Factors - genetics
