A New lncRNA, APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins

Negishi, Masamitsu; Wongpalee, Somsakul Pop; Sarkar, Sukumar; Park, Jonghoon; Lee, Kyung Yong; Shibata, Yoshiyuki; Reon, Brian J.; Abounader, Roger; Suzuki, Yutaka; Sugano, Sumio; Dutta, Anindya

doi:10.1371/journal.pone.0095216

Cited by 83 publications

(88 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These RNAs may work in gene regulatory networks as signals, decoys, guides or scaffold [46][47][48], and coordinate histone modifications by binding to various histone modification enzymes such as PRC2, which is a methyltransferase for H3K27me3 and is involved in the repression of gene transcription [49][50][51]. EZH2 is a catalytic subunit of PRC2 [52].…”

Section: Discussionmentioning

confidence: 99%

SNHG6 Promotes Tumor Growth via Repression of P21 in Colorectal Cancer

Qiu

Qiu³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: SNHG6 (Small Nucleolar RNA Host Gene 6) is a novel non-coding RNA (ncRNA) and its cellular function is largely unknown. Methods: Cell Counting Kit-8 (CCK-8) cell growth assay, colony formation and flow cytometry were used to determine colorectal cancer cell proliferation, cell cycle progression and apoptosis in vitro. The xenograft tumor formation assay in nude mice was established to evaluate tumor growth in vivo. RNA immunopreciptation (RIP) analysis was performed to examine whether SNHG6 could bind to EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), and chromatin immunoprecipitation (ChIP) assay was conducted to examine whether SNHG6 could repress p21 transcription by recruiting EZH2 to the p21 promoter. Results: Here we found that SNHG6 was upregulated and its expression levels were positively correlated with advanced tumor stage in colorectal cancer. Survival analysis suggested that higher expression of SNHG6 predicted poor prognosis in patients with colorectal cancer. Functional studies indicated that SNHG6 could promote cell proliferation via a direct suppression of p21 expression in colorectal cancer cells. Moreover, SNHG6 repressed p21 transcription through recruiting EZH2 to the p21 promoter in colorectal cancer cells. Conclusion: Taken together, our study demonstrates that SNHG6 promotes tumor growth via repression of p21 in colorectal cancer, which may provide a promising target for novel anticancer therapeutics.

show abstract

Section: Discussionmentioning

confidence: 99%

SNHG6 Promotes Tumor Growth via Repression of P21 in Colorectal Cancer

Qiu

Qiu³

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…While this paper was in press, another case of Alu-mediated DNA targeting of a lncRNA was published by Anindya Dutta and colleagues (Negishi et al 2014 …”

Section: Note Added In Proofmentioning

confidence: 99%

The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Johnson

Guigó

2014

RNA

280

231

View full text Add to dashboard Cite

Our genome contains tens of thousands of long noncoding RNAs (lncRNAs), many of which are likely to have genetic regulatory functions. It has been proposed that lncRNA are organized into combinations of discrete functional domains, but the nature of these and their identification remain elusive. One class of sequence elements that is enriched in lncRNA is represented by transposable elements (TEs), repetitive mobile genetic sequences that have contributed widely to genome evolution through a process termed exaptation. Here, we link these two concepts by proposing that exonic TEs act as RNA domains that are essential for lncRNA function. We term such elements Repeat Insertion Domains of LncRNAs (RIDLs). A growing number of RIDLs have been experimentally defined, where TE-derived fragments of lncRNA act as RNA-, DNA-, and protein-binding domains. We propose that these reflect a more general phenomenon of exaptation during lncRNA evolution, where inserted TE sequences are repurposed as recognition sites for both protein and nucleic acids. We discuss a series of genomic screens that may be used in the future to systematically discover RIDLs. The RIDL hypothesis has the potential to explain how functional evolution can keep pace with the rapid gene evolution observed in lncRNA. More practically, TE maps may in the future be used to predict lncRNA function.

show abstract

“…For example, LOC100505854 is overexpressed in the IDH2 R172 subset, but not in the IDH2 R140 samples. This lncRNA associates with and represses the tumor suppressor CDKN1A/p21 promoter by recruiting polycomb complex proteins (45).…”

Section: Lncrna Signatures Associated With Recurrent Mutations In Cn-mentioning

confidence: 99%

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Garzon

Volinia

Papaioannou

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

216

200

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides, located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis, and cell cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged ≥60 y) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. An independent set of 71 untreated older patients with CN-AML was used to validate the outcome scores using RNA sequencing. Distinctive lncRNA profiles were found associated with selected mutations, such as internal tandem duplications in the FLT3 gene (FLT3-ITD) and mutations in the NPM1, CEBPA, IDH2, ASXL1, and RUNX1 genes. Using the lncRNAs most associated with event-free survival in a training cohort of 148 older patients with CN-AML, we derived a lncRNA score composed of 48 lncRNAs. Patients with an unfavorable compared with favorable lncRNA score had a lower complete response (CR) rate [P < 0.001, odds ratio = 0.14, 54% vs. 89%], shorter disease-free survival (DFS) [P < 0.001, hazard ratio (HR) = 2.88] and overall survival (OS) (P < 0.001, HR = 2.95). The validation set analyses confirmed these results (CR, P = 0.03; DFS, P = 0.009; OS, P = 0.009). Multivariable analyses for CR, DFS, and OS identified the lncRNA score as an independent marker for outcome. In conclusion, lncRNA expression in AML is closely associated with recurrent mutations. A small subset of lncRNAs is correlated strongly with treatment response and survival

show abstract

A New lncRNA, APTR, Associates with and Represses the CDKN1A/p21 Promoter by Recruiting Polycomb Proteins

Cited by 83 publications

References 37 publications

SNHG6 Promotes Tumor Growth via Repression of P21 in Colorectal Cancer

SNHG6 Promotes Tumor Growth via Repression of P21 in Colorectal Cancer

The RIDL hypothesis: transposable elements as functional domains of long noncoding RNAs

Expression and prognostic impact of lncRNAs in acute myeloid leukemia

Contact Info

Product

Resources

About