Nemo-like kinase (NLK) primes colorectal cancer progression by releasing the E2F1 complex from HDAC1

Li, Shangze; Zeng, Feng; Li, Jun; Shu, Qi-Peng; Zhang, Huihui; Xu, Jun; Ren, Jianwei; Zhang, Xiaodong; Song, Xuemin; Du, Ran

doi:10.1016/j.canlet.2018.05.032

Cited by 25 publications

(19 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, we confirmed that circMAT2B could sequester and inhibit miR-610 activity by sponging endogenous miR-610, which targets the oncogene E2F1, which is related to cell proliferation, and is overexpression in a variety of human cancer including CRC. 31 – 33 Further studies showed that the down-regulation of miR-610 and the upregulation of E2F1 could effectively reverse the si-circMAT2B-mediated inhibition of proliferation in HCT116 and HT29 cells. Overall, our research confirmed that circMAT2B promoted CRC proliferation by sponging miR-610, which targets the oncogene E2F1.…”

Section: Discussionmentioning

confidence: 99%

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

Zhao

Chen

2020

CMAR

View full text Add to dashboard Cite

Purpose: Recently, studies have demonstrated that a novel circular RNA (circRNA), circMAT2B, can promote cell proliferation and can thus contribute to the growth and development of hepatocellular carcinoma. However, the precise mechanisms underlying in circMAT2B-induced colorectal cancer (CRC) cell proliferation are not yet fully understood. Materials and Methods: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circMAT2B expression in 70 CRC tissues and 70 matched adjacent normal tissues, CRC cell lines and human colonic epithelial cell line (NCM460). The direct interaction between miR-610 and circMAT2B or E2F1 was verified using luciferase reporter assay and biotinylated RNA Pull-down assay. Cell Counting Kit-8, colony formation assay, flow cytometry were utilized to examine the effect of circMAT2B, miR-610 and E2F1 on cell proliferation. Western blot was conducted to evaluate E2F1 expression. Results: In our study, circMAT2B was found to be upregulated in CRC tissues and cell lines. Furthermore, the silencing of circMAT2B significantly inhibited proliferation. Hence, in order to investigate the mechanism underlying the oncogenic properties of circMAT2B in CRC, a bioinformatics analysis (circular RNA Interactome, https://circinteractome.nia.nih. gov/) was performed to screen the putative interacting microRNAs of circMAT2B. miR-610 was identified to be one of the potential targeted miRNAs of circMAT2B. Luciferase reporter and RNA pulldown assay confirmed a direct interaction between circMAT2B and miR-610. Moreover, circMAT2B expression was negatively correlated with the expression of miR-610 in CRC tissues (r=−0.5131, p<0.0001). Furthermore, we demonstrated circMAT2B upregulated expression levels of the miR-610 target gene E2F1, which is involved in cell proliferation, is overexpression in a broad range of human cancer including CRC. Further studies suggested that E2F1 upregulation could significantly reverse the si-circMAT2B-mediated inhibition of proliferation. Conclusion: circMAT2B is upregulated in CRC tissues and cell lines. Moreover, circMAT2B promoted CRC proliferation by regulating the miR-610/E2F1 axis, which may serve as a potential therapeutic target for CRC treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

Zhao

Chen

2020

CMAR

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that NLK acts as a negative regulator of Notch signaling by phosphorylating Notch1-ICD and interfering with the formation of active Notch transcriptional complexes 29 . In addition, NLK is involved in nervous system development 30,31 and cancer cell proliferation 32–34 . Our group has shown that NLK regulates NF-kappa B signaling by disrupting the interaction of TAK1 with IKK 35 .…”

Section: Introductionmentioning

confidence: 99%

Phosphorylation of MAVS/VISA by Nemo-like kinase (NLK) for degradation regulates the antiviral innate immune response

Shu

Song

et al. 2019

Nat Commun

Self Cite

View full text Add to dashboard Cite

MAVS is essential for antiviral immunity, but the molecular mechanisms responsible for its tight regulation remain poorly understood. Here, we show that NLK inhibits the antiviral immune response during viral infection by targeting MAVS for degradation. NLK depletion promotes virus-induced antiviral cytokine production and decreases viral replication, which is potently rescued by the reintroduction of NLK. Moreover, the depletion of NLK promotes antiviral effects and increases the survival times of mice after infection with VSV. NLK interacts with and phosphorylates MAVS at multiple sites on mitochondria or peroxisomes, thereby inducing the degradation of MAVS and subsequent inactivation of IRF3. Most importantly, a peptide derived from MAVS promotes viral-induced IFN-β production and antagonizes viral replication in vitro and in vivo. These findings provide direct insights into the molecular mechanisms by which phosphorylation of MAVS regulates its degradation and influences its activation and identify an important peptide target for propagating antiviral responses.

show abstract

“…Among all these E2F family, E2F1 is the most extensively investigated member of E2F family in CRC [23][24][25]. A research reported suppressive function of E2F1 showed that the absence of E2F1 gene lead to an increased incidence and progression of tumorigenesis induced by PTEN loss [23].…”

Section: Discussionmentioning

confidence: 99%

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

Zhang¹,

Yang²,

Zhang³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: E2F family of transcription factors are related to cell cycle and apoptosis with activate or repress function on human cancer. Their critical role in colorectal cancer (CRC), including colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ), were widely investigated with contradictory and ambiguous results. Methods: In this study, we explored the expressions of these eight E2F genes and their predictive values on the overall survive (OS) and disease-free survival (DFS) in CRC patients by means of bioinformatic databases, such as ONCOMINE, GEPIA, DAVIA and cBioPortal.Results: We found that the transcriptional levels of E2F1/2/3/5/7/8 were significantly higher in CRC patients than that in normal samples, while the E2F4/6 showed no significantly difference from GEPIA database. The transcriptional levels of all eight E2F factors showed no correlation with four tumor stages, except for the E2F3 is significantly varied in COAD patients. Survival analysis based on GEPIA database indicated that lower E2F3 and E2F4 mRNA expressions were significantly associated with the OS of the COAD patients.Conclusions: This study manifested that the E2F1/2/3/5/7/8 are potential biomarkers of CRC patients, and E2F3 could be used as the predictive factor of tumor stage in COAD patients. E2F3 and E2F4 might be the prognostic markers for COAD patients.

show abstract

Nemo-like kinase (NLK) primes colorectal cancer progression by releasing the E2F1 complex from HDAC1

Cited by 25 publications

References 36 publications

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

<p>Circular RNA MAT2B Induces Colorectal Cancer Proliferation via Sponging miR-610, Resulting in an Increased E2F1 Expression</p>

Phosphorylation of MAVS/VISA by Nemo-like kinase (NLK) for degradation regulates the antiviral innate immune response

A Research of the Predictive Values of E2F Factors in Colorectal Cancer

Contact Info

Product

Resources

About