MicroRNA-486-5p enhances hepatocellular carcinoma tumor suppression through repression of IGF-1R and its downstream mTOR, STAT3 and c-Myc

Youness, R.A.; El-Tayebi, Hend Mohamed; Assal, R.A.; Hosny, Karim; Esmat, Gamal; Abdelaziz, Ahmed Ihab

doi:10.3892/ol.2016.4914

Cited by 74 publications

(89 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently we have shown that miR-486-5p could act as a tumor suppressor miRNA upon forcing its expression in HCC mainly through decreasing IGF-1/IGF-1R axis and its downstream mediators mTOR, STAT3, c-MYC [17]. On the other hand previous studies have shown that c-MYC regulates the expression of let-7a [16], which in turn regulates IGF2BP1 [19,20].…”

Section: Discussionmentioning

confidence: 97%

“…This was attributed to its ability to stabilize the c-MYC and MKI67 mRNAs and increase their protein expression levels [15].On the other hand c-Myc was shown to be an upstream regulator to many miRNAs and validated as a repressor for let-7a [16], which highlights a potential feedback loop between c-Myc, Let-7a and IGF2BP1. suppressor miRNA through directly targeting IGF-1, IGF-1R and its downstream signaling mediators c-Myc, mTOR, STAT3 in Huh-7 cells [17,18].Thus hypothetically miR-486-5p may regulate IGF2BP1 through the manipulation of the expression of c-MYCLet-7a axis, so the main aim of this study was to investigate the interplay between c-Myc and Let-7a via miR-486-5p and its impact on IGF2BP1.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Perturbation of IGF2BP1 Transcriptome upon the Interplay between miR-486-5p and let-7a

Abdelaziz¹,

Ha²,

Ra³

et al. 2017

JGPLD

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

Perturbation of IGF2BP1 Transcriptome upon the Interplay between miR-486-5p and let-7a

Abdelaziz¹,

Ha²,

Ra³

et al. 2017

JGPLD

Self Cite

View full text Add to dashboard Cite

“…Let‐7a can enhance the sensitivity of HCC to cetuximab via regulating STAT3 (Xue et al, ). miR‐486‐5p inhibits HCC progression through repression of STAT3 (Youness et al, ). LncRNA00364 can repress HCC development via modulating p‐STAT3‐IFIT2 signaling (Tang et al, ).…”

Section: Discussionmentioning

confidence: 99%

LINC01433 promotes hepatocellular carcinoma progression via modulating the miR‐1301/STAT3 axis

Huang¹,

Zhang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in hepatocellular carcinoma (HCC) tumor progression. LINC01433 has been implicated in the progression of lung cancer. However, its biological role in HCC remains poorly understood. In our current study, we focused on the detailed mechanism of LINC01433 in HCC development. First, it was exhibited that LINC01433 was remarkably elevated in HCC cells, which indicated that LINC01433 was involved in HCC. Then, knockdown of LINC01433 was able to restrain HCC cell proliferation and cell colony formation and greatly induced cell apoptosis. On the contrary, overexpression of LINC01433 promoted HCC cell proliferation, increased cell colony formation, and enhanced cell invasion capacity. Subsequently, we found that miR-1301 was remarkably decreased in HCC cells, and it can serve as a target of LINC01433 according to bioinformatics analysis. In addition, the binding correlation between them was validated by performing RNA pull-down experiments and RIP assay. Moreover, STAT3 was predicted and validated as a target of miR-1301, and it was shown that miR-1301 mimics significantly suppressed STAT3 in HCC cells.Finally, in vivo models were established, and the results demonstrated that silencing of LINC01433 could repress HCC development through modulating miR-1301 and STAT3. Taken together, these results indicated in our study that LINC01433 participated in HCC progression through modulating the miR-1301/STAT3 axis and it might act as a novel biomarker in HCC diagnosis and treatment.

show abstract

“…Importantly, ANK1 hypermethylation inhibits the transcription of miR-486 [164], which may have pathogenic consequences as suppression of this miRNA has pro-inflammatory consequences and is furthermore associated with increased cellular survival and proliferation [165,166]. Furthermore, upregulation of miR-486 acts as a negative regulator of Akt (protein kinase B), mTOR and STAT3 (signal transducer and activator of transcription 3), all of which play major roles in microglial activation, proliferation and survival [167,168].…”

Section: Epigenetic Dysregulation Of Ank1 As a Source Of Microglial Pmentioning

confidence: 99%

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

et al. 2018

View full text Add to dashboard Cite

The classical amyloid cascade model for Alzheimer's disease (AD) has been challenged by several findings. Here, an alternative molecular neurobiological model is proposed. It is shown that the presence of the APOE ε4 allele, altered miRNA expression and epigenetic dysregulation in the promoter region and exon 1 of TREM2, as well as ANK1 hypermethylation and altered levels of histone post-translational methylation leading to increased transcription of TNFA, could variously explain increased levels of peripheral and central inflammation found in AD. In particular, as a result of increased activity of triggering receptor expressed on myeloid cells 2 (TREM-2), the presence of the apolipoprotein E4 (ApoE4) isoform, and changes in ANK1 expression, with subsequent changes in miR-486 leading to altered levels of protein kinase B (Akt), mechanistic (previously mammalian) target of rapamycin (mTOR) and signal transducer and activator of transcription 3 (STAT3), all of which play major roles in microglial activation, proliferation and survival, there is activation of microglia, leading to the subsequent (further) production of cytokines, chemokines, nitric oxide, prostaglandins, reactive oxygen species, inducible nitric oxide synthase and cyclooxygenase-2, and other mediators of inflammation and neurotoxicity. These changes are associated with the development of amyloid and tau pathology, mitochondrial dysfunction (including impaired activity of the electron transport chain, depleted basal mitochondrial potential and oxidative damage to key tricarboxylic acid enzymes), synaptic dysfunction, altered glycogen synthase kinase-3 (GSK-3) activity, mTOR activation, impairment of autophagy, compromised ubiquitin-proteasome system, iron dyshomeostasis, changes in APP translation, amyloid plaque formation, tau hyperphosphorylation and neurofibrillary tangle formation.

show abstract

MicroRNA-486-5p enhances hepatocellular carcinoma tumor suppression through repression of IGF-1R and its downstream mTOR, STAT3 and c-Myc

Cited by 74 publications

References 43 publications

Perturbation of IGF2BP1 Transcriptome upon the Interplay between miR-486-5p and let-7a

Perturbation of IGF2BP1 Transcriptome upon the Interplay between miR-486-5p and let-7a

LINC01433 promotes hepatocellular carcinoma progression via modulating the miR‐1301/STAT3 axis

Could Alzheimer’s Disease Originate in the Periphery and If So How So?

Contact Info

Product

Resources

About