Bidirectional transcription of Linc00441 and RB1 via H3K27 modification-dependent way promotes hepatocellular carcinoma

Tang, Junwei; Xie, Yu; Xu, Xiaoliang; Yin, Yin; Jiang, Runqiu; Deng, Lei; Tan, Zhongming; Gangarapu, Venkatanarayana; Tang, Jinhai; Sun, Beicheng

doi:10.1038/cddis.2017.81

Cited by 35 publications

(29 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast, some HCC-promoting lncRNAs are induced by activated epigenetic marks. Tang et al reported that the upregulation of linc00441 expression was due to enhanced H3K27 acetylation [76]. Overexpressed linc00441 in turn recruits DNMT3A to methylate and inactivate its neighbor gene RB1, thereby promoting the proliferation of HCC cells [76].…”

Section: Epigenetic Modificationmentioning

confidence: 99%

The role of long noncoding RNAs in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most frequent subtype of primary liver cancer and one of the leading causes of cancer-related death worldwide. However, the molecular mechanisms underlying HCC pathogenesis have not been fully understood. Emerging evidences have recently suggested the crucial role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of HCC. Various HCC-related lncRNAs have been shown to possess aberrant expression and participate in cancerous phenotypes (e.g. persistent proliferation, evading apoptosis, accelerated vessel formation and gain of invasive capability) through their binding with DNA, RNA or proteins, or encoding small peptides. Thus, a deeper understanding of lncRNA dysregulation would provide new insights into HCC pathogenesis and novel tools for the early diagnosis and treatment of HCC. In this review, we summarize the dysregulation of lncRNAs expression in HCC and their tumor suppressive or oncogenic roles during HCC tumorigenesis. Moreover, we discuss the diagnostic and therapeutic potentials of lncRNAs in HCC.

show abstract

Section: Epigenetic Modificationmentioning

confidence: 99%

The role of long noncoding RNAs in hepatocellular carcinoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…An example of this class of lncRNA is Linc00441 , the bidirectional transcribed lncRNA of the Retinoblastoma gene RB1 . Linc00441 has recently been reported to be aberrantly upregulated and inversely correlated to RB1 expression in human HCC samples [ 46 ]. More specifically, Linc00441 has also been reported to epigenetically suppress RB1 expression in HCC by recruiting DNMT3A methyltransferase [ 46 ].…”

Section: Lncrnas: Characteristics and Subclassificationmentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Hepatocarcinogenesis

Lanzafame

Bianco

Terracciano

et al. 2018

IJMS

View full text Add to dashboard Cite

Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being “transcriptional noise”, increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.

show abstract

“…Dysfunction of the pRb pathway is detected in every type of cancer. To date, a few lncRNAs have been identified to regulate the pRb pathway and G1/S transition, and their deregulation has been shown to affect tumor growth . Obviously, it is highly worthwhile to identify more lncRNAs that regulate the pRb pathway.…”

mentioning

confidence: 99%

Lnc‐UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9‐Mediated CDK6 Down‐regulation

et al. 2019

View full text Add to dashboard Cite

Although thousands of long noncoding RNAs (lncRNAs) have been annotated, only a limited number of them have been functionally characterized. Here, we identified an oncogenic lncRNA, named lnc‐UCID (lncRNA up‐regulating CDK6 by interacting with DHX9). Lnc‐UCID was up‐regulated in hepatocellular carcinoma (HCC), and a higher lnc‐UCID level was correlated with shorter recurrence‐free survival of HCC patients. Both gain‐of‐function and loss‐of function studies revealed that lnc‐UCID enhanced cyclin‐dependent kinase 6 (CDK6) expression and thereby promoted G1/S transition and cell proliferation. Studies from mouse xenograft models revealed that tumors derived from lnc‐UCID‐silenced HCC cells had a much smaller size than those from control cells, and intratumoral injection of lnc‐UCID small interfering RNA suppressed xenograft growth. Mechanistically, the 850‐1030‐nt domain of lnc‐UCID interacted physically with DEAH (Asp‐Glu‐Ala‐His) box helicase 9 (DHX9), an RNA helicase. On the other hand, DHX9 post‐transcriptionally suppressed CDK6 expression by binding to the 3′‐untranslated region (3′UTR) of CDK6 mRNA. Further investigation disclosed that lnc‐UCID enhanced CDK6 expression by competitively binding to DHX9 and sequestering DHX9 from CDK6‐3′UTR. In an attempt to explore the mechanisms responsible for lnc‐UCID up‐regulation in HCC, we found that the lnc‐UCID gene was frequently amplified in HCC. Furthermore, miR‐148a, whose down‐regulation was associated with an increase of lnc‐UCID in HCC, could bind lnc‐UCID and inhibit its expression. Conclusion: Up‐regulation of lnc‐UCID, which may result from amplification of its gene locus and down‐regulation of miR‐148a, can promote HCC growth by preventing the interaction of DHX9 with CDK6 and subsequently enhancing CDK6 expression. These findings provide insights into the biological functions of lncRNAs, the regulatory network of cell cycle control, and the mechanisms of HCC development, which may be exploited for anticancer therapy.

show abstract

Bidirectional transcription of Linc00441 and RB1 via H3K27 modification-dependent way promotes hepatocellular carcinoma

Cited by 35 publications

References 55 publications

The role of long noncoding RNAs in hepatocellular carcinoma

The role of long noncoding RNAs in hepatocellular carcinoma

The Role of Long Non-Coding RNAs in Hepatocarcinogenesis

Lnc‐UCID Promotes G1/S Transition and Hepatoma Growth by Preventing DHX9‐Mediated CDK6 Down‐regulation

Contact Info

Product

Resources

About