NUDT21 regulates 3′-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma

Sun, Meng; Ding, Jian; Li, Dali; Yang, Guoping; Zhang, Cheng; Zhu, Qubo

doi:10.1016/j.canlet.2017.09.026

Cited by 52 publications

(52 citation statements)

References 27 publications

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“…MiRNAs have been reported to be subsistent in the cytoplasm in the form of miRNA ribonucleoprotein complexes (miRNPs). Ago2, as an important component of miRNPs constituent proteins, took part in composing RNA induced silencing complex (RISC) [35]. Similar results were obtained from RNA binding protein immunoprecipitation assay (RIP) where Ago2 antibody enriched immunoprecipitation emerged more abundant MEG3 and miR-181a RNA compared with the control group (Fig.…”

Section: Meg3 Binds To Mir-181a In MM Cellssupporting

confidence: 75%

Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

Shen

Bai

Zhu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Long non-coding RNA maternally expressed gene 3 (MEG3) has been reported to play an essential role in cancer progression and metastasis. However, the overall biological role and regulatory mechanism of MEG3 in multiple myeloma (MM) development and progression remains largely ill-defined. Methods: MEG3 and miR-181a expression of MM patients were analyzed by publicly available MM data sets. Cell counting kit-8 and flow cytometry analysis were used to identify the function of MEG3 on MM in vitro. Additionally, we conducted tumor formation experiments in mice models to explain the role of MEG3 on MM in vivo. Then, several mechanism experiments, including dual-luciferase reporter assay and RNA immunoprecipitation were performed to evaluate the emulative relationship between MEG3 and miR-181a. Results: In this research, we found that MEG3 was downregulated in MM patients, which was linked with tumor progression. In addition, we demonstrated that miR-181a was overexpressed in MM patients in consistent with its cancer-promoting function. Importantly, several mechanism experiments revealed that MEG3, acting as an endogenous competitive RNA, could contend with miR-181a to inhibit tumor progression. Furthermore, as the target mRNA of miR-181a, homeobox gene A11(HOXA11) could be positively regulated by MEG3 through sponging miR-181a competitively in vitro. Conclusion: Our present work supplies the first discovery of a MEG3/miR-181a/HOXA11 regulatory network in MM and highlights that MEG3 may serve as a promising target for MM therapy in the future.

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Section: Meg3 Binds To Mir-181a In MM Cellssupporting

confidence: 75%

Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

Shen

Bai

Zhu

et al. 2018

Cell Physiol Biochem

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“…28 In this study, we investigated the mechanistic basis for F I G U R E 6 EZH2 is important for trophoblast growth and migration and endothelial cell tube formation. 13 They confirmed the role of NUDT21 in APA and miRNA-mediated gene silencing. After 24 h, EZH2 overexpressing HTR8/SVneo cells were transfected with miR-138-5p or miR-363-3p mimics to down-regulated EZH2 expressing.…”

Section: Discussionmentioning

confidence: 68%

“…13 Down-regulation of Nudt21 expression in cells has been reported to lead to changes in alternative poly(A) site utilization for several somatic mRNAs. 13 Down-regulation of Nudt21 expression in cells has been reported to lead to changes in alternative poly(A) site utilization for several somatic mRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…13 A luciferase activity assay then revealed that the miRNA-mediated inhibition of luciferase activity was abolished after the UGUA sequences in the 3'-UTR had been mutated (P < 0.1 compared with Ezh2 wild-type) ( Figure 5H,I). 13 A luciferase activity assay then revealed that the miRNA-mediated inhibition of luciferase activity was abolished after the UGUA sequences in the 3'-UTR had been mutated (P < 0.1 compared with Ezh2 wild-type) ( Figure 5H,I).…”

Section: Nudt21 Increases the Efficiency Of Mirmediated Ezh2 Silencingmentioning

confidence: 98%

“…11,12 For example, in hepatocellular carcinoma (HCC), it was previously shown that shortening of the 3'-UTRs of various oncogenes effectively removed miRNA binding sites enabling these genes to evade miRNA regulation, become overexpressed, and induce tumorigenesis and metastasis. 13 NUDT21 (also known as CPSF5 and CFIM25) is a highly conserved hydrolase that forms one subunit of the cleavage factor Im complex (CFIM) required for 3' RNA cleavage and polyadenylation processing, which are early steps in the assembly of eukaryotic pre-mRNA. 14,15 It has previously been shown that knockdown of NUDT21 leads to changes in alternative poly(A) site utilization promoting the selection of the proximal ploy(A) site and thereby shortening the 3'-UTRs of several somatic mRNAs.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The role of NUDT21 in microRNA‐binding sites of EZH2 gene increases the risk of preeclampsia

Xiao

Zhao²,

Huang

et al. 2019

J Cellular Molecular Medi

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Objectives Preeclampsia (PE) is a major cause of mortality and morbidity among pregnant mothers and their fetuses worldwide. Recent studies have shown that several microRNAs (miRNAs) play crucial role in pathogenesis of PE patients; however, the mechanisms responsible for differences in miRNA function in PE largely remain to be determined. Materials and Methods We studied that NUDT21 expression was markedly increased, whereas EZH2 was decreased in placental samples from patients with PE. We identified NUDT21 as an interaction partner of enhancer of zeste homologue 2 (EZH2). NUDT21 co‐localized with EZH2 in the human trophoblast cell line, HTR‐8/SVneo and NUDT21 was shown to bind to EZH2 in RNA immunoprecipitation assays. NUDT21 has previously been reported to be involved in alternative polyadenylation; thus, the interaction between NUDT21 and EZH2 may play an important role in the crosstalk between alternative polyadenylation (APA) and miRNA‐mediated gene silencing in PE. Results In the human trophoblast cell line HTR‐8/SVneo, loss‐of‐function assays indicated that knockdown of NUDT21 suppressed cell proliferation, migration and tube formation. Furthermore, functional studies showed that NUDT21 elongated the 3'‐UTR of mRNAs thereby exposing more miRNA binding sites (including miR138 and miR363), which enhanced the efficiency of miRNA‐mediated gene silencing and promoted EZH2 binding. Conclusions This is the first report about the relationship of NUDT21 and EZH2. The data indicate that the aberrant expression of NUDT21 contributes to PE by targeting 3'‐UTR of EZH2 mRNA. These findings may provide novel targets for future investigations into therapeutic strategies for PE.

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Target Reprogramming the 3′UTR of Tumor‐Suppressor Genes by a siRNA Composite Nanoparticle for Glioblastoma Therapy

Gu,

Zeng,

Gong

et al. 2024

Adv Funct Materials

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Glioblastoma multiforme (GBM) is the most aggressive and common adult brain tumor. Current therapies primarily involve surgical resection, followed by chemotherapy and radiotherapy. However, the low survival rate due to high toxicity, side effects, and poor targeting necessitates novel treatments. Post‐transcriptional regulation pathways, particularly the regulation of alternative polyadenylation based on the mRNA 3′UTR, play a critical role in cell growth and development and the progression of tumors. Targeting tumor cells and reprogramming the 3′UTR of tumor suppressor genes to achieve post‐transcriptional regulation is expected to be a new channel for GBM therapy. Herein, a novel siRNA delivery system is developed based on mesoporous silica nanoparticles: siRNA composite nanoparticles (siRNA CNP). Encapsulation in MSNs overcomes siRNA degradation and cellular entry issues, while lipid bilayer coating improves biocompatibility and stability. Surface‐modified nucleic acid aptamer SL1 (Apt‐SL1) significantly enhances GBM targeting, offering therapeutic potential. The findings show that siRNA CNP effectively silences the promoter CFIm25 of distal poly(A) in tumor cells, inducing gene reprogramming, inhibiting tumor growth, and promoting apoptosis in nude mice. The siRNA CNP demonstrates a significant effect in reprogramming tumor suppressor genes and treating GBM. It offers a novel and promising therapeutic avenue for GBM.

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NUDT21 regulates 3′-UTR length and microRNA-mediated gene silencing in hepatocellular carcinoma

Cited by 52 publications

References 27 publications

Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

Long Non-Coding RNA MEG3 Functions as a Competing Endogenous RNA to Regulate HOXA11 Expression by Sponging miR-181a in Multiple Myeloma

The role of NUDT21 in microRNA‐binding sites of EZH2 gene increases the risk of preeclampsia

Target Reprogramming the 3′UTR of Tumor‐Suppressor Genes by a siRNA Composite Nanoparticle for Glioblastoma Therapy

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