| RRC ID |
76701
|
| 著者 |
Taiji Hamada, Michiyo Higashi, Seiya Yokoyama, Toshiaki Akahane, Masanori Hisaoka, Hirotsugu Noguchi, Tatsuhiko Furukawa, Akihide Tanimoto
|
| タイトル |
MALAT1 functions as a transcriptional promoter of MALAT1::GLI1 fusion for truncated GLI1 protein expression in cancer
|
| ジャーナル |
BMC Cancer
|
| Abstract |
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.
|
| 巻・号 |
23
|
| 公開日 |
2023-5-10
|
| DOI |
10.1186/s12885-023-10867-6
|
| PMID |
37165307
|
| IF |
3.15
|
| リソース情報 |
| 遺伝子材料 |
pGL4-phGLI1 (RDB07902)
pcDNA3.1-His-hGLI1 (RDB08063)
Genome Network Project Human cDNA clone IRAL011L19 (HGY084683) |
