Targeting Pin1 by inhibitor API‐1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development

Pu, Wenchen; Jiao, Li; Zheng, Yuanyuan; Shen, Xianyan; Fan, Xin; Zhou, Jian‐Kang; He, Jinzhi; Deng, Yulan; Liu, Xuesha; Wang, Chun; Yang, Shengyong; Chen, Qiang; Liu, Lunxu; Zhang, Guolin; Wei, Yuquan; Peng, Yong

doi:10.1002/hep.29819

Cited by 60 publications

(66 citation statements)

References 50 publications

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“…miRNAs are involved in nearly every fields of cellular processes like proliferation, apoptosis, metabolism, and autophagy [22,23,25,26]. So many diseases have been investigated to be associated with miRNA expression [35,36].…”

Section: Discussionmentioning

confidence: 99%

“…miRNAs are a number of small noncoding RNAs with 20~24 nucleotides that inhibit gene expression, such as mRNA degradation and translational inhibition, by binding the 3 ′ UTR region of mRNA [24]. miRNAs have been recorded to regulate cell proliferation, metastasis [25], apoptosis [22,26], and autophagy [23]. Recently, the role of miRNAs in age-related cataract has been noted.…”

Section: Introductionmentioning

confidence: 99%

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Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Huang

Zhou

et al. 2020

BioMed Research International

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Background. Oxidative stress is an important factor during age-related cataract formation. Apoptosis and autophagy induced by oxidative stress have been reported as key factors in age-related cataract. In our research, we investigated the role of let-7c-3p in the regulation of autophagy and apoptosis during the formation of age-related cataract. Material and Methods. Real-time PCR and western blot were employed to detect the expression of let-7c-3p in the tissues of age-related cataract. Human lens epithelial cells (LECs) were treated with H2O2 as an age-related cataract model. The extent of apoptosis was measured by flow cytometry and western blot. To detect autophagy, immunofluorescence was used to analyze the spot number of LC3, and western blot was used to detect the expression of LC3-II/I and ATG3. The molecular mechanisms of let-7c-3p regulating autophagy via ATG3 under oxidative stress were performed by a luciferase report gene assay and rescue experiment. Results. Downregulation of let-7c-3p was found in the age-related cataract group aged >65 years relative to the age-related cataract group aged ≤65 years. Consistently, the expression of let-7c-3p was also lower under oxidative stress. The activities of LEC apoptosis and autophagy induced by oxidative stress were inhibited by let-7c-3p. By the bioinformatics database and the luciferase reporter assay, ATG3 was found to be a direct target of let-7c-3p. Let-7c-3p reduced the ATG3-mediated autophagy level, which was induced by oxidative stress in LECs. Conclusion. Let-7c-3p inhibits autophagy by targeting ATG3 in LECs in age-related cataract.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Huang

Zhou

et al. 2020

BioMed Research International

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“…To test the pXPO5 dependence of AF-39,w ec haracterizedt he anti-proliferative activity of AF-39 in Huh7-CTL (low XPO5 phosphorylation) and Huh7-MEKDD( high XPO5 phosphorylation) cells. [10] As in Figure S3, the activity of AF-39 was sharply reduced when pXPO5w as at al ow level, indicating the pXPO5 dependance of AF-39.U nlike ATRA [9] and KPT-6566, [7] AF-39 did not induce Pin1 degradation( Figure S4). These resultsp rovideda potentialmechanism forthe anti-cancer effect of AF-39 in HCC cells.…”

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confidence: 81%

“…[9] Recently,6 -O-benzylguanine derivative API-1h ave been found to locate into Pin1 PPIase domain and suppress Pin1 function in vitro and in vivo. [10] However,t he study on the small molecular Pin1 inhibitors is still in their infancy, and no Pin1 inhibitors have been applied to clinical treatment against solid tumors,including hepatocellular carcinoma (HCC).…”

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confidence: 99%

Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis

Zheng

Jiao

et al. 2018

Chemistry An Asian Journal

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Peptidyl-prolyl cis-trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently,w eh ave disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy.H ere, 7-(benzyloxy)-3,5-dihydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4H-chromen-4-one (AF-39)w as identified as an ovel Pin1 inhibitor.B iochemical tests indicate that AF-39 potently inhibits Pin1 activity with an IC 50 values of 1.008 mm,a nd also displays high selectivity for Pin1 among peptidyl prolyli somerases. Furthermore, AF-39 significantly suppresses cell proliferation of HCC cells in ad ose-and time-dependent manner. Mechanistically, AF-39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides ap romising lead compound for HCC treatment, highlighting the therapeutic potentialo f miRNA-based therapy against human cancer.

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“…The incidence rate of hepatocellular carcinoma (HCC) ranks in the sixth, and lethality ranks in the third place worldwide [1]. And there is no obvious symptoms in the early stages and HCC holds fast development and metastasis.…”

Section: Introductionmentioning

confidence: 99%

A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway

Bao

Yuan

et al. 2018

Cell Physiol Biochem

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Background/Aims: The roles and related mechanisms of RNA binding protein FUS (fused in sarcoma/translocated in liposarcoma) are unclear in numerous cancers, including hepatocellular carcinoma (HCC). Methods: Quantitative reverse transcription PCR (qRT-PCR), western blot, cell viability, transwell migration and invasion, tumor spheres formation and in vivo tumor formation assays were used to examine the effects of FUS on HCC progression in HuH7 and MHCC97 cells. Additionally, transcriptome analysis based on RNA-sequencing data, qRT-PCR, western blots, luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays were used to explore the LATS1/2 (large tumor suppressor kinases 1/2)-related mechanisms contributing to FUS functions. Finally, qRT-PCR and western blot analysis were used to detect the levels of FUS and LATS1/2 in HCC and adjacent normal tissues, and the correlation between them in HCC tissues. Results: Overexpression of FUS decreased cell viability, migration, invasion and stemness. Moreover, FUS interacted and stabilized LATS1/2 stability, and thus promoted LATS1/2 expression and activated Hippo pathway. Finally, FUS and LAST1/2 levels were positively correlated and significantly down-regulated in HCC tissues. Conclusion: We demonstrate that FUS/LATS1/2 axis inhibits HCC progression via activating Hippo pathway.

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Targeting Pin1 by inhibitor API‐1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development

Cited by 60 publications

References 50 publications

Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells

Discovery of a Prenylated Flavonol Derivative as a Pin1 Inhibitor to Suppress Hepatocellular Carcinoma by Modulating MicroRNA Biogenesis

A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway

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