PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

Zhang, Hui; Sheng, Cheng; Yin, Yi; Wen, Shu; Yang, Guoping; Zhang, Cheng; Zhu, Qubo

doi:10.1016/j.canlet.2015.07.010

Cited by 66 publications

(59 citation statements)

References 27 publications

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“…In addition, PABPC1 plays the most important role in deadenylation and protects poly (A) tail by covering the poly (A) tail. Previous studies show that PABPC1 interacts with AGO2 and is responsible for the microRNA‐mediated gene silencing 32. In addition, PABPC1 also directly participate in gastric cancer tumorigenesis by influencing cell proliferation 33.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies show that PABPC1 interacts with AGO2 and is responsible for the microRNA-mediated gene silencing. 32 In addition, PABPC1 also directly participate in gastric cancer tumorigenesis by influencing cell proliferation. 33 These studies strongly suggest that PABPC1 may play an oncogenic role in cancer progression under the regulation of SNHG14.…”

Section: Discussionmentioning

confidence: 99%

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Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation

Huang

Wang

et al. 2018

J Cellular Molecular Medi

101

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Currently, resistance to trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor, has become one major obstacle for improving the clinical outcome of patients with advanced HER2+ breast cancer. While cell behaviour can be modulated by long non‐coding RNAs (lncRNAs), the contributions of lncRNAs in progression and trastuzumab resistance of breast cancer are largely unknown. To this end, the involvement and regulatory functions of lncRNA SNHG14 in human breast cancer were investigated. RT‐qPCR assay showed that SNHG14 was up‐regulated in breast cancer tissues and associated with trastuzumab response. Gain‐ and loss‐of‐function experiments revealed that overexpression of SNHG14 promotes cell proliferation, invasion and trastuzumab resistance, whereas knockdown of SNHG14 showed an opposite effect. PABPC1 gene was identified as a downstream target of SNHG14, and PABPC1 mediates the SNHG14‐induced oncogenic effects. More importantly, ChIP assays demonstrated that lncRNA SNHG14 may induce PABPC1 expression through modulating H3K27 acetylation in the promoter of PABPC1 gene, thus resulting in the activation of Nrf2 signalling pathway. These data suggest that lncRNA SNHG14 promotes breast cancer tumorigenesis and trastuzumab resistance through regulating PABPC1 expression through H3K27 acetylation. Therefore, SNHG14 may serve as a novel diagnostic and therapeutic target for breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation

Huang

Wang

et al. 2018

J Cellular Molecular Medi

101

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“…Co-immunoprecipitation (Co-IP) assays in human embryonic kidney 293 (HEK293) cells confirmed the interaction between TTR and PABPC1 ( Figure 2A); in hRECs, western blot analysis indicated that PABPC1 levels increased with TTR, while lncRNA-MEG3 overexpression or knockdown showed no significant effects on the PABPC1 level with TTR ( Figure 2B) in high-glucose environments. Previous studies demonstrated that PABPC1 participates in regulation pathways and lncRNA stabilization [33][34][35]. To investigate whether PABPC1 regulated the stability of lncRNA-MEG3, actinomycin D was used to inhibit RNA synthesis in hRECs.…”

Section: Ttr Interacted With Poly(a) Binding Protein Cytoplasmic 1 (Pmentioning

confidence: 99%

“…In our previous work using miRNA microarray and qRT-PCR assays, miR223-3p was upregulated in serum and aqueous humor of DR patients, and TTR was proved to affect neovascularization in DR through the STAT4/miR-223-3p/FBXW7 signaling pathway [32]. However, how lncRNA-MEG3 interacts with TTR in DR remains to be explored.As the interaction between lncRNA-MEG3 and miR223-3p has been reported in human aortic endothelial cells (HAECs) [30], in the current study we aim to investigate: (1) the potential relationship between TTR and lncRNA-MEG3; and (2) the relationship between lncRNA-MEG3 and poly(A) binding protein cytoplasmic 1 (PABPC1), on the basis that the co-immunoprecipitator, PABPC1, has been identified as the direct binding target of TTR and has been reported to bind the poly (A) tails of mRNAs, regulating the stability and biofunction of lncRNAs [33][34][35],.This study was designed to elucidate the details of the interactions between TTR and miR223-3p, including the potential direct targets of TTR (PABPC1) and miR223-3p (lncRNA-MEG3) in DR, both in vivo and in vitro, which might provide new principles on the molecular pathogenesis, clinical prevention, and therapy of DR.…”

mentioning

confidence: 99%

“…As the interaction between lncRNA-MEG3 and miR223-3p has been reported in human aortic endothelial cells (HAECs) [30], in the current study we aim to investigate: (1) the potential relationship between TTR and lncRNA-MEG3; and (2) the relationship between lncRNA-MEG3 and poly(A) binding protein cytoplasmic 1 (PABPC1), on the basis that the co-immunoprecipitator, PABPC1, has been identified as the direct binding target of TTR and has been reported to bind the poly (A) tails of mRNAs, regulating the stability and biofunction of lncRNAs [33][34][35],.…”

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confidence: 99%

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Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Fan

Zhang

et al. 2019

IJMS

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The aim of the study was to demonstrate how transthyretin (TTR) could affect long non-coding RNA (lncRNA) of maternally expressed gene 3 (MEG3) and play important roles in diabetic retinopathy (DR). A DR model in C57BL/6 mice was established after intraperitoneal injection of streptozotocin (STZ). After intravitreal injection with TTR pAAV vector, MEG3 short hairpin RNA (shRNA), scrambled shRNA, or MEG3, retinal imaging, retinal trypsin digestion, and fundus vascular permeability tests were performed. Cell counting kit-8 (CCK8), transwell, and Matrigel assays were employed to detect the proliferation and migration of human retinal microvascular endothelial cells (hRECs). The binding between long non-coding RNA of maternally expressed gene 3 (lncRNA-MEG3) and microRNA-223-3p (miR-223-3p) was observed by using luciferase reporter assays, while co-immunoprecipitation (co-IP) was employed to confirm the interaction between TTR and the target. In the DR mice model, retinal vascular leakage and angiogenesis were repressed by overexpressing TTR. In vitro, the added TTR promoted the level of lncRNA-MEG3 by interacting with poly (A) binding protein cytoplasmic 1 (PABPC1), and then repressed proliferation and angiogenesis of hRECs. In vivo, silencing or overexpressing lncRNA-MEG3 significantly affected retinal vascular phenotypes. Additionally, the interaction between lncRNA-MEG3 and miR-223-3p was confirmed, and silencing of miR-223-3p revealed similar effects on hRECs as overexpression of lncRNA-MEG3. In summary, in the DR environment, TTR might affect the lncRNA MEG3/miR-223-3p axis by the direct binding with PABPC1, and finally repress retinal vessel proliferation.Keywords: diabetic retinopathy (DR); transthyretin (TTR); long non-coding RNA (lncRNA); maternally expressed gene 3 (MEG3); polyadenylate-binding protein cytoplasmic 1 (PABPC1) Int.In the eyes, transthyretin (TTR) is mainly expressed in human retinal pigment epithelial cells (hRPECs) and the choroid [7], and it usually works as the carrier of thyroxine (T4) and retinol [8,9]. As previously reported, TTR should be correlated with diabetes-associated diseases, e.g., type I diabetes patients showed lower serum TTR levels [10]. In clinical investigations, myopia was revealed to protect diabetic patients from suffering DR [11,12]. Our previous work has demonstrated that higher vitreous TTR content of high myopia patient [13] might help to prevent the progression of DR [14]. The serum and vitreous TTR levels in DR patients were associated with DR progression [15]; TTR suppressed angiogenesis by affecting the angiopoietin-Tie signaling pathway in hyperglycemia [16], and enhanced the apoptosis of hRECs through a hypoxia-associated 78-kDa glucose-regulated protein (GRP78)-dependent pathway [17]. Still, the regulatory mechanisms involving TTR in DR are not entirely clear.Long non-coding RNAs (lncRNAs) regulate targeted mRNA expression via the microRNA (miRNA) response element known as competing endogenous RNA (ceRNA) [18,19]. LncRNAs are known to play vital roles in oc...

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Exosome miR‐335 as a novel therapeutic strategy in hepatocellular carcinoma

et al. 2018

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Hepatocellular carcinoma (HCC) is a common and deadly cancer. Most cases of HCC arise in a cirrhotic/fibrotic liver, indicating that environment may play a paramount role in cancer genesis. Previous studies from our group and others have shown that, in desmoplastic cancers, there is a rich intercellular communication between activated, cancer-associated fibroblasts and cancer cells. Moreover, extracellular vesicles (EVs), or exosomes, have been identified as an important arm of this intercellular communication platform. Finally, these studies have shown that EVs can carry microRNA (miR) species in vivo and deliver them to desmoplastic cancers. The precise role played by activated liver fibroblasts/stellate cells in HCC development is insufficiently known. Based on previous studies, it appears plausible that activated fibroblasts produce signals carried by EVs that promote HCC genesis. In the current study, we first hypothesized and then demonstrated that stellate cell-derived EVs 1) can be loaded with an miR species of choice (miR-335-5p); 2) are taken up by HCC cells in vitro and more importantly in vivo; 3) can supply the miR-335-5p cargo to recipient HCC cells in vitro as well as in vivo; and 4) inhibit HCC cell proliferation and invasion in vitro as well as induce HCC tumor shrinkage in vivo. Finally, we identified messenger RNA targets for miR-335 that are down-regulated after treatment with EV-miR-335-5p. This study informs potential therapeutic strategies in HCC, whereby stellate cell-derived EVs are loaded with therapeutic nucleic acids and delivered in vivo. (Hepatology 2018;67:940-954).

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PABPC1 interacts with AGO2 and is responsible for the microRNA mediated gene silencing in high grade hepatocellular carcinoma

Cited by 66 publications

References 27 publications

Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation

Long non‐coding RNA SNHG14 induces trastuzumab resistance of breast cancer via regulating PABPC1 expression through H3K27 acetylation

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

Exosome miR‐335 as a novel therapeutic strategy in hepatocellular carcinoma

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