Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Lin, Xianzhi; Spindler, Tassja J.; Fonseca, Marcos Abraão de Souza; Corona, Rosario I.; Seo, Ji-Heui; Dezem, Felipe Segato; Li, Lewyn; Lee, Janet M.; Long, Henry W.; Sellers, Thomas A.; Karlan, Beth Y.; Noushmehr, Houtan; Freedman, Matthew L.; Gayther, Simon A.; Lawrenson, Kate

doi:10.1016/j.isci.2019.06.025

Cited by 62 publications

(60 citation statements)

References 73 publications

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“…In the cytoplasm, phosphorylated AMOT binds as a scaffold to MST1/2, LATS1/2 and YAP/TAZ, promoting their phosphorylation and preventing YAP/TAZ nuclear translocation [100][101][102]. However, in some cancers, including renal, hepatic and ovarian cancer, there is also evidence for a YAP-activating role of AMOT in the nucleus [103,104], and a recent study identified the involvement of an AMOT-binding long noncoding RNA in this nuclear activity [105]. In addition, tight junction protein 2 (TJP2/ZO-2) promotes the nuclear translocation of YAP/TAZ through interaction with the PDZ domain [106,107].…”

Section: Yap and Taz-functionally Redundant?mentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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YAP and TAZ are intracellular messengers communicating multiple interacting extracellular biophysical and biochemical cues to the transcription apparatus in the nucleus and back to the cell/tissue microenvironment interface through the regulation of cytoskeletal and extracellular matrix components. Their activity is negatively and positively controlled by multiple phosphorylation events. Phenotypically, they serve an important role in cellular plasticity and lineage determination during development. As they regulate self-renewal, proliferation, migration, invasion and differentiation of stem cells, perturbed expression of YAP/TAZ signaling components play important roles in tumorigenesis and metastasis. Despite their high structural similarity, YAP and TAZ are functionally not identical and may play distinct cell type and differentiation stage-specific roles mediated by a diversity of downstream effectors and upstream regulatory molecules. However, YAP and TAZ are frequently looked at as functionally redundant and are not sufficiently discriminated in the scientific literature. As the extracellular matrix composition and mechanosignaling are of particular relevance in bone formation during embryogenesis, post-natal bone elongation and bone regeneration, YAP/TAZ are believed to have critical functions in these processes. Depending on the differentiation stage of mesenchymal stem cells during endochondral bone development, YAP and TAZ serve distinct roles, which are also reflected in bone tumors arising from the mesenchymal lineage at different developmental stages. Efforts to clinically translate the wealth of available knowledge of the pathway for cancer diagnostic and therapeutic purposes focus mainly on YAP and TAZ expression and their role as transcriptional co-activators of TEAD transcription factors but rarely consider the expression and activity of pathway modulatory components and other transcriptional partners of YAP and TAZ. As there is a growing body of evidence for YAP and TAZ as potential therapeutic targets in several cancers, we here interrogate the applicability of this concept to bone tumors. To this end, this review aims to summarize our current knowledge of YAP and TAZ in cell plasticity, normal bone development and bone cancer.Cells 2020, 9, 972 2 of 34 co-activators Yes-associated protein 1 (YAP-1, YAP) and its paralogue, the transcriptional co-activator with PDZ-binding motif (TAZ, WWTR1), which are typically controlled on the post-translational level by upstream regulatory signaling pathways in organ development and tissue homeostasis [2,3]. YAP and TAZ were reported to affect self-renewal and lineage commitment of stem cells [4][5][6][7], while hyperactivation of YAP and TAZ have been linked to cancer growth and metastasis in various tumors [8][9][10]. TAZ levels are elevated in approximately 20% of cancers and drive invasion and metastasis [11,12], while YAP is frequently overexpressed or amplified in cancer and was shown to promote resistance to chemotherapy in oncogene-addicted tumors up...

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Section: Yap and Taz-functionally Redundant?mentioning

confidence: 99%

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Kovar

Bierbaumer

Radic-Sarikas

2020

Cells

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“…In addition, seRNA functions an indispensable role in tumorigenesis through mediating activation of oncogenic signaling pathways, which participates in cell proliferation, autophagy, apoptosis, EMT, ECM remodeling, and angiogenesis. It has been confirmed that seRNA from urothelial cancer associated 1 (UCA1) promotes ovarian cancer development through interacting with angiomotin (AMOT) to activate yes-associated protein (YAP) signaling [34]. To comprehensively clarify the functional mechanisms of seRNA in promoting cancer progression, we systematically introduced seRNA generation and its characteristics, inducible factors of seRNA and their molecular mechanisms in cancer progress.…”

Section: Introductionmentioning

confidence: 99%

Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis

Tan

Tang

2020

Mol Cancer

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seRNA is a noncoding RNA (ncRNA) transcribed from active super-enhancer (SE), through which SE exerts biological functions and participates in various physiological and pathological processes. seRNA recruits cofactor, RNA polymerase II and mediator to constitute and stabilize chromatin loop SE and promoter region, which regulates target genes transcription. In tumorigenesis, DNA insertion, deletion, translocation, focal amplification and carcinogen factor mediate oncogenic SE generation, meanwhile, oncogenic SE transcribes into tumor-related seRNA, termed as oncogenic seRNA. Oncogenic seRNA participates in tumorigenesis through activating various signal-pathways. The recent reports showed that oncogenic seRNA implicates in a widespread range of cytopathological processes in cancer progression including cell proliferation, apoptosis, autophagy, epithelial-mesenchymal transition, extracellular matrix stiffness and angiogenesis. In this article, we comprehensively summarized seRNA's characteristics and functions, and emphatically introduced inducible formation of oncogenic seRNA and its functional mechanisms. Lastly, some research strategies on oncogenic seRNA were introduced, and the perspectives on cancer therapy that targets oncogenic seRNA were also discussed.

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“…However, they can have important post-translational effects by modulating the half-lives of the proteins they bind by stabilizing them, as in the case of ABHD11-AS1 and RhoC [10]; DANCR and UPF1 [11]; and FAM83H-AS1 and HuR [15]. UCA1 can act as a scaffold between two proteins; e.g., for cytoplasmic Yes-associated protein (YAP) and angiomotin, it promotes YAP dephosphorylation and its translocation to the nucleus to act as a transcription coactivator [157]. Other examples of post-translational regulation are the lncRNA HAL, which interacts with Twist1, this interaction being important for promoting EMT [126], and the lncRNA HULC, which interacts with ATG7 and inhibits the autophagy pathway [6].…”

Section: Post-translational Regulationmentioning

confidence: 99%

“…Some signaling pathways that trigger lncRNA transcription have also been identified; for instance, CXCL14 produced by surrounding fibroblasts triggers LINC00092 transcription [31]; TGF-β1 activates MALAT1 [21], PTAR [154] and PTAL [153] transcription; or pEGFR activates ABHD11-AS1 through STAT3 [136]. The lncRNA UCA1 has been described as being activated by a super-enhancer [157].…”

Section: Regulation Of Lncrna Expressionmentioning

confidence: 99%

The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use

Salamini-Montemurri

Lamas-Maceiras

Barreiro-Alonso

et al. 2020

Cancers

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Ovarian cancer is one of the most lethal gynecological malignancies worldwide because it tends to be detected late, when the disease has already spread, and prognosis is poor. In this review we aim to highlight the importance of long non-coding RNAs (lncRNAs) in diagnosis, prognosis and treatment choice, to make progress towards increasingly personalized medicine in this malignancy. We review the effects of lncRNAs associated with ovarian cancer in the context of cancer hallmarks. We also discuss the molecular mechanisms by which lncRNAs become involved in cellular physiology; the onset, development and progression of ovarian cancer; and lncRNAs' regulatory mechanisms at the transcriptional, post-transcriptional and post-translational stages of gene expression. Finally, we compile a series of online resources useful for the study of lncRNAs, especially in the context of ovarian cancer. Future work required in the field is also discussed along with some concluding remarks.

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Super-Enhancer-Associated LncRNA UCA1 Interacts Directly with AMOT to Activate YAP Target Genes in Epithelial Ovarian Cancer

Cited by 62 publications

References 73 publications

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

The YAP/TAZ Pathway in Osteogenesis and Bone Sarcoma Pathogenesis

Oncogenic seRNA functional activation: a novel mechanism of tumorigenesis

The Challenges and Opportunities of LncRNAs in Ovarian Cancer Research and Clinical Use

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