DPEP1 is a direct target of miR-193a-5p and promotes hepatoblastoma progression by PI3K/Akt/mTOR pathway

Cui, Xichun; Liu, Xin; Han, Qicai; Zhu, Jianming; Li, Jianhao; Ren, Zhigang; Liu, Liwen; Luo, Yanbing; Wang, Zhifang; Zhang, Dandan; Fan, Yun; Zhang, Da; Dong, Gang

doi:10.1038/s41419-019-1943-0

Cited by 32 publications

(36 citation statements)

References 30 publications

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“…Upregulation of DPEP1 was found in human HBs and was associated with poor prognosis. 115 Many additional pathways were found to be involved in HB tumorigenesis, growth, and progression, such as NOTCH, 116 Jak/Stat, 117 Ras, 118 and TGF-β. 119 Further studies are needed to elucidate the specific function(s) of these cascades in human HB.…”

Section: Igf Pathwaymentioning

confidence: 99%

Molecular Mechanisms of Hepatoblastoma

et al. 2021

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Hepatoblastoma (HB) is the predominant primary liver tumor in children. While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt/β-catenin pathway activation in this disease. Nonetheless, β-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Perturbations of several pathways, including Hippo, Hedgehog, NRF2/KEAP1, HGF/c-Met, NK-1R/SP, and PI3K/AKT/mTOR cascades and aberrant activation of c-MYC, n-MYC, and EZH2 proto-oncogenes, have been identified in HB, although their role requires additional investigation. Here, we summarize the current knowledge on HB molecular pathogenesis, the relevance of the preclinical findings for the human disease, and the innovative therapeutic strategies that could be beneficial for the treatment of HB patients.

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Section: Igf Pathwaymentioning

confidence: 99%

Molecular Mechanisms of Hepatoblastoma

et al. 2021

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“…MiRNAs are short, non-coding RNAs which play crucial roles in regulating gene expression mainly through binding to the 3′ untranslated region (3′UTR) of target mRNAs 8 , 9 . A growing body of evidence suggests that miRNAs are important tumor regulators and play a critical role in the tumorigenesis 10 . They have been emerged as novel therapeutic targets to control the initiation and progress of cancers 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and the therapeutic outcomes remain undesirable. Increasing evidence shows that aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) plays crucial roles in tumorigenesis of multiple tumors. However, the expression status and functions of ARNTL2 in PDAC remain elusive. Here we showed that ARNTL2 expression was markedly upregulated in PDAC tissues and cell lines. elevated expression of ARNTL2 was positively related to unfavorable prognosis. Knockdown of ARNTL2 could suppress motility and invasive ability of PDAC cells in vitro, as well as tumor development in vivo. In addition, microRNA-26a-5p (miR-26a-5p) was identified as the crucial specific arbitrator for ARNTL2 expression and the expression of miR-26a-5p was inversely correlated with ARNTL2 expression in PDAC tissues. Functionally, elevated expression of miR-26a-5p was found to inhibit the proliferation, migration, and invasion of PDAC cells in vitro, while ARNTL2 increased expression could partially abolish the suppressive effect of miR-26a-5p. Mechanism study indicated that elevated expression of miR-26a-5p suppressed TGF/BETA signaling pathway by targeting ARNTL2 in PDAC cells. In conclusion, our data suggested that ARNTL2 acted as an oncogene to regulate PDAC growth. MiR-26a-5p/ARNTL2 axis may be a novel therapeutic candidate target in PDAC treatment.

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“…mTOR is a key regulator and can be activated by phosphorylated-AKT. The activation of AKT-mTOR is found to be important in contributing to the fibrosis in different organs, including the lungs, liver, and heart (Wang et al, 2015 ; Reilly et al, 2017 ; Cui et al, 2019 ; Wan et al, 2019 ), which can regulate cell growth and promote EMT in the kidney (Yoo et al, 2011 ; Xuan et al, 2014 ; Carpenter et al, 2015 ; Yang et al, 2015 ). Furthermore, the activation of ERK1/2 also significantly contributes to the onset of EMT (Chiu et al, 2017 ; Sankpal et al, 2017 ; Jia et al, 2018 ; Lee et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial–Mesenchymal Transition

Zhang

Yin

Sun

et al. 2021

Front. Cell Dev. Biol.

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Kidney fibrosis is generally confirmed to have a significant role in chronic kidney disease, resulting in end-stage kidney failure. Epithelial–mesenchymal transition (EMT) is an important molecular mechanism contributing to fibrosis. Tubular epithelial cells (TEC), the major component of kidney parenchyma, are vulnerable to different types of injuries and are a significant source of myofibroblast by EMT. Furthermore, TRPC6 knockout plays an anti-fibrotic role in ameliorating kidney damage. However, the relationship between TRPC6 and EMT is unknown. In this study, TRPC6−/− and wild-type (WT) mice were subjected to a unilateral ureteric obstruction (UUO) operation. Primary TEC were treated with TGF-β1. Western blot and immunofluorescence data showed that fibrotic injuries alleviated with the inhibition of EMT in TRPC6−/− mice compared to WT mice. The activation of AKT-mTOR and ERK1/2 pathways was down-regulated in the TRPC6−/− mice, while the loss of Na+/K+-ATPase and APQ1 was partially recovered. We conclude that TRPC6 knockout may ameliorate kidney fibrosis by inhibition of EMT through down-regulating the AKT-mTOR and ERK1/2 pathways. This could contribute to the development of effective therapeutic strategies on chronic kidney diseases.

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DPEP1 is a direct target of miR-193a-5p and promotes hepatoblastoma progression by PI3K/Akt/mTOR pathway

Cited by 32 publications

References 30 publications

Molecular Mechanisms of Hepatoblastoma

Molecular Mechanisms of Hepatoblastoma

ARNTL2 promotes pancreatic ductal adenocarcinoma progression through TGF/BETA pathway and is regulated by miR-26a-5p

Transient Receptor Potential Channel 6 Knockout Ameliorates Kidney Fibrosis by Inhibition of Epithelial–Mesenchymal Transition

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