Loss of the basic helix-loop-helix transcription factor Bhlhe41 induces cell death and impairs neurite outgrowth in Neuro2a cells

Sun, Yuxin; Zhang, Haina; Wang, Libo; Li, Jia; Jin, Hui; Wang, Zhenyu; Tian, Shiyuan; Qi, Ling; Liu, Xiaoyang

doi:10.1007/s11010-018-3383-z

Cited by 6 publications

(6 citation statements)

References 25 publications

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“…31 Class E basic helix−loop−helix protein 41 (Bhlhe41), also known as BHLHB3 or SHARP-1, was involved in various cellular functions, such as differentiation, proliferation, tumorigenesis, and cicradian rhythms. 32 Signal transducer and activator of transcription 3 (Stat3) plays a vital role in many processes, such as apoptosis, cell growth, and response to cytokine. Recent research indicated that Stat3 played a dominant role in inflammation by regulating IL-10 33 and the polarization of macrophages/microglia in the traumatic brain injury brain.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Systematic Study of Crucial Transcription Factors of Coptidis rhizoma Alkaloids against Cerebral Ischemia-Reperfusion Injury

Zhou

Guo

Xiang

et al. 2021

ACS Chem. Neurosci.

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Coptidis rhizoma alkaloids (CRAs), extracted from Coptidis rhizoma, have been indicated to play important neuroprotective roles, but the mechanism underlying has not been determined, especially from the perspective of transcription factors (TFs). In this study, crucial TFs involved in the protective activity of CRA were revealed based on RNA-Seq technology, proteomics, and network pharmacological analysis of the effects of CRA on middle cerebral artery occlusion-mediated cerebral ischemia-reperfusion (I/R) injury. Importantly, CRA significantly reduced the infarction rate and neurological deficiency score. Moreover, CRA significantly decreased the levels of TNF-α, MCP-1, and IL-1β. In addition, seven TFs, including Ncor1, Smad1, Bhlhe41, Stat3, Sp100, Satb2, and Lrpprc, were found to be crucial TFs, and five of these TFs were associated with inflammation. Furthermore, eight compounds in CRA were associated with the identified TFs through network pharmacological analysis. The alteration of Lrpprc and Sabt2 was further confirmed by measuring their downstream genes, including Pigg, Hhatl, Wdr77, Mpped1, Arpp21, Ppfia3, Rims1, and Cacna2d1 by reverse transcriptase polymerase chain reaction. Thus, these seven TFs may be important targets in CRA-mediated protection against I/R injury. This research provides a new view of the protective effect of CRA against cerebral I/R injury and reveals new therapeutic targets for treating cerebral ischemia.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Systematic Study of Crucial Transcription Factors of Coptidis rhizoma Alkaloids against Cerebral Ischemia-Reperfusion Injury

Zhou

Guo

Xiang

et al. 2021

ACS Chem. Neurosci.

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“…That marker was adjacent to the BHLHE41 (basic helix-loop-helix family member e41) gene. BHLHE41 is known to be a transcription factor implicated in cellular functions such as proliferation, differentiation, and tumorigenesis 27 . It is possible that this marker is linked to genetic factors that directly or indirectly affect the expression of the BHLHE41 gene.…”

Section: Discussionmentioning

confidence: 99%

“…In the GWAS, the most highly associated marker was rs10842679 (P = 4.7E-07). The gene nearest rs10842679 was BHLHE41, which is known as a putative regulator of neuronal differentiation 27 . Interestingly, markers located in the 3'UTR of the HIVEP3 gene showed a strong association with telomere length (Table 3).…”

Section: Genetic Association Analysis Of Telomere Lengthmentioning

confidence: 99%

Clinical Significance of Germline Telomere Length and Associated Genetic Factors in Patients with Neuroblastoma

Sung

Bae

Lee

et al. 2022

Preprint

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Background: Studies investigating the relationship between germline telomere length and the clinical characteristics of tumors are very limited. This study evaluated the relationship between germline telomere length and the clinical characteristics of neuroblastoma. In addition, a genome-wide association study (GWAS) was performed to investigate the genetic factors associated with telomere length. Methods: The telomere length of peripheral blood mononuclear cells from 186 patients with neuroblastoma was measured by quantitative PCR. The association between germline telomere length and clinical characteristics, including long-term survival, was investigated. For the GWAS, genotyping was performed with a high-density Illumina bead chip. After strict quality control checks of the samples, an association analysis was conducted. Results: An extra-abdominal primary site, lower stage (stage 1/2), MYCN non-amplified tumor, and being in the low-risk group were associated with longer telomere lengths (P = 0.015, 0.007, 0.046 and 0.042, respectively). Patients with longer third telomeres had longer event-free survival than other patients (P = 0.032). In the GWAS, rs2492082, located in the 3’UTR of the HIVEP3 gene, showed the highest association with telomere length (P = 1.7E-06). Patients with long telomeres had a recessive allele A. A gene-based analysis using the VEGAS2 algorithm showed that the CNTN4 gene had the most significant association with telomere length (P = 1.0E-06). Patients with the CC homozygote in the rs71311728 marker within the CNTN4 gene had a longer telomere length than those with the TC heterozygote. A gene ontology analysis showed that genetically susceptible genes associated with telomere length were mainly distributed in neurite morphogenesis and neuron development.Conclusions: Longer germline telomere length is associated with favorable prognostic factors at diagnosis and eventually better event-free survival in patients with neuroblastoma. In addition, the GWAS demonstrated that genetic markers and genes related to telomere length are associated with neurite morphogenesis and neuron development. A further study with a larger cohort of patients and functional studies are needed.

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“…It has the greatest expression abundance in the central nervous system 25. Recent studies indicate that oscillatory bHLH factor expression is important in nervous system development 26 , 27. Sun et al demonstrated that BHLHE41 plays critical roles in regulating cell death and Neuro2a cell neurite outgrowth 28.…”

Section: Discussionmentioning

confidence: 99%

<p>BHLHE41 promotes U87 and U251 cell proliferation via ERK/cyclinD1 signaling pathway</p>

Wang¹,

Zhao²,

Zheng³

et al. 2019

CMAR

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Purpose The biological functions of BHLHE41 in the proliferation of glioblastoma remained unexplored. We aimed to investigate the biological roles and underlying molecular mechanisms of BHLHE41 in glioblastoma. Materials and methods We used multiple methods, including Western blot analysis, soft agar colony-formation assay, CCK8 assay, and flow cytometry, to evaluate the changes in multiple cellular functions after BHLHE41 knockdown or overexpression in U87 and U251 cell lines. The TCGA database was then used to analyze the associations between BHLHE41 expression with clinicopathological factors and the overall survival (OS) of glioma patients. Results This study determined that overexpression of BHLHE41 promoted glioma cell proliferation and colony formation. Besides, BHLHE41 upregulated cyclinD1, cyclinD3, and cyclinE1 expression and drove phase transition from G1 to S and G2 phases by upregulating these cyclins. In contrast, knockdown of BHLHE41 had an opposite effect on all of these parameters. However, BHLHE41 had no effect on apoptosis. Moreover, BHLHE41 activated MAPK/ERK signaling pathway to upregulate cyclinD1 expression. After the ERK signal pathway was blocked by a specific inhibitor, SCH772984, cyclinD1 upregulation was reversed. Furthermore, the median OS of low-grade glioma (LGG) patients with low to median level of BHLHE41 was 22.6 months, longer than that of the patients with high level of BHLHE41 (21.0 months). Conclusion BHLHE41 has an important role in the proliferation of glioblastoma and could serve as a novel candidate for targeted therapy of glioblastoma.

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Loss of the basic helix-loop-helix transcription factor Bhlhe41 induces cell death and impairs neurite outgrowth in Neuro2a cells

Cited by 6 publications

References 25 publications

Systematic Study of Crucial Transcription Factors of Coptidis rhizoma Alkaloids against Cerebral Ischemia-Reperfusion Injury

Systematic Study of Crucial Transcription Factors of Coptidis rhizoma Alkaloids against Cerebral Ischemia-Reperfusion Injury

Clinical Significance of Germline Telomere Length and Associated Genetic Factors in Patients with Neuroblastoma

<p>BHLHE41 promotes U87 and U251 cell proliferation via ERK/cyclinD1 signaling pathway</p>

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