Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3

Ni, Weijian; Yao, Su; Zhou, Yunxia; Liu, Yuanyuan; Huang, Pinbo; Zhou, Anni; Li, Jingwen; Che, Li-Heng; Li, Jianming

doi:10.1186/s12943-019-1079-y

Cited by 425 publications

(297 citation statements)

References 38 publications

Supporting

Mentioning

296

Contrasting

Order By: Relevance

“…LncRNA GAS5 enhances YAP phosphorylation to increase ubiquitination and degradation of it, thereby impairing YAP signaling and inhibiting colorectal cancer (CRC) cell proliferation and metastasis. YTHDF3 recognizes m6A modified GAS5 and induces decay of it [92].…”

Section: Ythdf3mentioning

confidence: 99%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

822

675

View full text Add to dashboard Cite

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

show abstract

Section: Ythdf3mentioning

confidence: 99%

Functions of N6-methyladenosine and its role in cancer

et al. 2019

Mol Cancer

822

675

View full text Add to dashboard Cite

show abstract

“…Interestingly, Ni et al discovered a negative functional loop of lncRNA GAS5/YAP/YTHDF3 axis in CRC [50]. GAS5 could promote YAP to translocate from nucleus to cytoplasm, and facilitate YAP phosphorylation, ubiquitination and degradation, thus inhibiting CRC progression.…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

“…And YAP targeted at the promoter of YTHDF3, leading to an increase of YTHDF3 expression. Then, YTHDF3 recognized m 6 A-containing GAS5 and accelerated its degradation, further affecting the activity of YAP signaling pathway in CRC [50].…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

“…Increasing the expression of β-catenin, WNT6 and FZD9A to activate Wnt/β-catenin pathway [49] YTHDF3 GAS5 Enhancing the degradation of lncRNA GAS5 [50] YTHDC1 circNSUN2 Facilitating circNSUN2 export from nucleus to cytoplasm [51] IGF2BP2 HMGA2 Forming a circNSUN2/IGF2BP2 complex to fortify the stability of HMGA2 [51] IGF2BP2 SOX2 Stabilizing SOX2 mRNA [52] Gastric cancer IGF2BP1 SEC62 Augmenting SEC62 mRNA translation [53] IGF2BP3 HDGF Facilitating HDGF mRNA expression [54] HuR ZMYM1 Fortifying the stability of ZMYM1 mRNA [116] Lung cancer YTHDF1 CDK2, CDK4, cyclinD1…”

Section: Conclusion and Perspectivementioning

confidence: 99%

See 1 more Smart Citation

m6A-binding proteins: the emerging crucial performers in epigenetics

et al. 2020

View full text Add to dashboard Cite

N 6 -methyladenosine (m 6 A) is a well-known post-transcriptional modification that is the most common type of methylation in eukaryotic mRNAs. The regulation of m 6 A is dynamic and reversible, which is erected by m 6 A methyltransferases ("writers") and removed by m 6 A demethylases ("erasers"). Notably, the effects on targeted mRNAs resulted by m 6 A predominantly depend on the functions of different m 6 A-binding proteins ("readers") including YT521-B homology (YTH) domain family, heterogeneous nuclear ribonucleoproteins (HNRNPs), and insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs). Indeed, m 6 A readers not only participate in multiple procedures of RNA metabolism, but also are involved in a variety of biological processes. In this review, we summarized the specific functions and underlying mechanisms of m 6 A-binding proteins in tumorigenesis, hematopoiesis, virus replication, immune response, and adipogenesis.

show abstract

“…Recently, emerging evidence has suggested that lncRNAs play a vital role in cellular development and human diseases, especially in cancer [12]. Dysregulated expression of lncRNAs might lead to progressive, uncontrolled growth and metastasis of tumors [14,34].…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal carcinogenesis by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

Wang

Chen

Shi

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Long noncoding RNAs (lncRNAs) are considered critical regulators in cancers; however, the clinical significance and mechanisms of MAPKAPK5-AS1 (MK5-AS1) in colorectal cancer (CRC) remain mostly unknown.Methods: In this study, quantitative real-time PCR ( qPCR ) and western blotting were utilized to detect the levels of MK5-AS1, let-7f-1-3p and MK5 (MAPK activated protein kinase 5) in CRC tissues and cell lines. The biological functions of MK5-AS1, let-7f-1-3p and MK5 in CRC cells were explored using Cell Counting Kit-8 ( CCK8 ), colony formation and transwell assays. The potential mechanisms of MK5-AS1 were evaluated by RNA pull-down, RNA immunoprecipitation ( RIP ), dual luciferase reporter assay, chromatin immunoprecipitation ( CHIP ) and bioinformatics analysis. The effects of MK5-AS1 and MK5 on CRC were investigated by a xenotransplantation model. Results : We confirmed that MK5-AS1 was significantly increased in CRC tissues. Knockdown of MK5-AS1 suppressed cell migration and invasion in vitro and inhibited lung metastasis in mice. Mechanistically, MK5-AS1 regulated SNAI1 expression by sponging let-7f-1-3p and cis -regulated the adjacent gene MK5. Moreover, MK5-AS1 recruited RBM4 and eIF4A1 to promote the translation of MK5. Our study verified that MK5 promoted the phosphorylation of c-Jun, which activated the transcription of SNAI1 by directly binding to its promoter.Conclusions : MK5-AS1 cis -regulated the nearby gene MK5 and acted as a let-7f-1-3p sponge, playing a vital role in CRC tumorigenesis. This study could provide novel insights into molecular therapeutic targets of CRC.

show abstract

Long noncoding RNA GAS5 inhibits progression of colorectal cancer by interacting with and triggering YAP phosphorylation and degradation and is negatively regulated by the m6A reader YTHDF3

Cited by 425 publications

References 38 publications

Functions of N6-methyladenosine and its role in cancer

Functions of N6-methyladenosine and its role in cancer

m6A-binding proteins: the emerging crucial performers in epigenetics

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal carcinogenesis by cis-regulating the nearby gene MK5 and acting as a let-7f-1-3p sponge

Contact Info

Product

Resources

About