| RRC ID |
52539
|
| 著者 |
Suzuki S, Hoshino H, Yoshida K, Nakanishi J, Tsuchiya-Hirata S, Kobuke S, Haruyama N, Nishimura F, Shiba H.
|
| タイトル |
Genome-wide identification of chromatin-enriched RNA reveals that unspliced dentin matrix protein-1 mRNA regulates cell proliferation in squamous cell carcinoma.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Chromatin-enriched noncoding RNAs (ncRNAs) have emerged as key molecules in epigenetic processes by interacting with chromatin-associated proteins. Recently, protein-coding mRNA genes have been reported to be chromatin-tethered, similar with ncRNA. However, very little is known about whether chromatin-enriched mRNA is involved in the chromatin modification process. Here, we comprehensively examined chromatin-enriched RNA in squamous cell carcinoma (SQCC) cells by RNA subcellular localization analysis, which was a combination of RNA fractionation and RNA-seq. We identified 11 mRNAs as highly chromatin-enriched RNAs. Among these, we focused on the dentin matrix protein-1 (DMP-1) gene because its expression in SQCC cells has not been reported. Furthermore, we clarified that DMP-1 mRNA was retained in chromatin in its unspliced form in SQCC in vitro and in vivo. As the inhibition of the unspliced DMP-1 mRNA (unspDMP-1) expression resulted in decreased cellular proliferation in SQCC cells, we performed ChIP-qPCR to identify cell cycle-related genes whose expression was epigenetically modified by unspDMP-1, and found that the CDKN1B promoter became active in SQCC cells by inhibiting unspDMP-1 expression. This result was further validated by the increased CDKN1B gene expression in the cells treated with siRNA for unspDMP-1 and by restoration of the decreased cellular proliferation rate by simultaneously inhibiting CDKN1B expression in SQCC cells. Further, to examine whether unspDMP-1 was able to associate with the CDKN1B promoter region, SQCC cells stably expressing PP7-mCherry fusion protein were transiently transfected with the unspDMP-1 fused to 24 repeats of the PP7 RNA stem loop (unspDMP-1-24xPP7) and we found that unspDMP-1-24xPP7 was efficiently precipitated with the antibody against mCherry and was significantly enriched in the CDKN1B promoter region. Thus, unspDMP-1 is a novel chromatin-enriched RNA that epigenetically regulates cellular proliferation of SQCC.
|
| 巻・号 |
495(3)
|
| ページ |
2303-2309
|
| 公開日 |
2018-1-15
|
| DOI |
10.1016/j.bbrc.2017.12.136
|
| PII |
S0006-291X(17)32536-6
|
| PMID |
29278708
|
| MeSH |
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology*
Cell Line, Tumor
Cell Proliferation / genetics*
Chromatin / genetics*
Chromosome Mapping / methods
Extracellular Matrix Proteins / genetics*
Humans
MicroRNAs / genetics
Phosphoproteins / genetics*
RNA, Neoplasm / genetics*
RNA, Untranslated / genetics*
|
| IF |
2.985
|
| 引用数 |
1
|
| リソース情報 |
| ヒト・動物細胞 |
Ca9-22(RCB1976)
HO-1-u-1(RCB2102)
HSC-2(RCB1945) |
