miR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer

Wang, Hui; Hu, Hui; Luo, Zhenzhao; Liu, Shuiyi; Wu, Wangze; Zhu, Man; Wang, Jing; Liu, Yingle; Lu, Zhongxin

doi:10.1042/bsr20200796

Cited by 16 publications

(12 citation statements)

References 25 publications

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Section: Discussionmentioning

confidence: 99%

“…These published results were consistent with our current findings. However, NUDT21 was identified to be a tumor suppressor in human cervical cancer (22), bladder cancer (23), lung cancer (including small cell lung cancer and non-small cell lung cancer) (24-26), breast cancer (16,27,28), and hepatocellular carcinoma (15,29,30). Moreover, the role of NUDT21 in human glioma was controversial: Jia-Cheng et al reported that NUDT21 was up-regulated in human glioma tissues, and NUDT21 promoted the proliferation of glioma cells through the NF-kB signaling pathway (31); in Chu Y et al's study, they identified that NUDT21 regulated the alternative polyadenylation of Pak1 and reduced expression of NUDT21 predicted worse survival in low grade glioma and glioblastoma patients (32).…”

Section: Nudt21 Stimulated Cell Proliferation and Metastasis In Gastric Cancer Cells Via Up-regulating Sgpp2mentioning

confidence: 99%

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NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

Zhu

Zhang

et al. 2021

Front. Oncol.

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Gastric cancer is one of the major malignancies with poor survival outcome. In this study, we reported that NUDT21 promoted cell proliferation, colony formation, cell migration and invasion in gastric cancer cells. The expression levels of NUDT21 were found to be much higher in human gastric cancer tissues compared with normal gastric tissues. NUDT21 expression was positively correlated with tumor size, lymph node metastasis and clinical stage in gastric cancer patients. High level of NUDT21 was associated with poor overall survival (OS) rates in gastric cancer patients. The expression levels of NUDT21 were also much higher in gastric cancer tissues from patients with tumor metastasis compared with those of patients without tumor metastasis. Moreover, forced expression of NUDT21 in gastric cancer cells promoted tumor growth and cell proliferation in xenograft nude mice, and depletion of NUDT21 in gastric cancer cells restrained lung metastasis in vivo. Through high throughput RNA-sequencing, SGPP2 was identified to be positively regulated by NUDT21 and mediated the tumor promoting role of NUDT21 in gastric cancer cells. Therefore, NUDT21 played an oncogenic role in human gastric cancer cells. NUDT21 could be considered as a novel potential target for gastric cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Nudt21 Stimulated Cell Proliferation and Metastasis In Gastric Cancer Cells Via Up-regulating Sgpp2mentioning

confidence: 99%

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

Zhu

Zhang

et al. 2021

Front. Oncol.

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“…These two miRNAs were grouped together in this platform because the mature sequence of miR-7975 differs by only one base from miR-4454 ( 37 ). Previous reports showed that miR-4454 promotes inflammation or cancer invasion and migration ( 38 , 39 ). However, the role of either miR-4454 or miR-7975 in breast milk for infants’ health and development is relatively unknown.…”

Section: Discussionmentioning

confidence: 97%

Extracellular vesicle miRNAs in breast milk of obese mothers

et al. 2022

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BackgroundBreast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) are expected to interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Thus, in mothers with obesity, miRNAs in bEVs can be altered, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of mothers with obesity and their potential impact on breastfed infants.MethodsWe recruited healthy nursing mothers who were either of normal weight (BMI < 25) or with obesity (BMI ≥ 30) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior 6 months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find differentially expressed miRNAs in bEVs of mothers with obesity compared to mothers of normal weight.ResultsWe included 65 nursing mothers: 47 of normal weight and 18 with obesity based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of various EV markers. Out of 37 EV markers, CD326 (EpCaM) was the most highly expressed in bEVs. The most abundant miRNAs in bEVs include miR-30b-5p, miR-4454, miR-494-3p, and let-7 miRNAs. Target genes of the top 10 miRNAs were associated with cancer, prolactin pathway, EGFR, ErbB, and FoxO signaling pathway. In bEVs of mothers with obesity, 19 miRNAs were differentially expressed (adjusted p < 0.05 cut-off), which include miR-575, miR-630, miR-642a-3p, and miR-652-5p. These miRNAs and their target genes were associated with neurological diseases and psychological disorders.ConclusionIn this study, we characterized bEVs and demonstrated altered miRNAs in bEVs of mothers with obesity and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.

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“…After comparing the thin and obese individuals, hsa-miR-4454 was consistently higher in obesity ( 48 ); whereas hsa-miR-582-5p was down-regulated in the visceral adipose tissues-derived exosomes of obese patients ( 49 ). They were found to be associated with diabetes and multiple cancer ( 50 , 51 ). In addition, angiogenin is a stress-induced secreted ribonuclease with nuclear and cellular solute activities, and involved in normal development and disease ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of plasma-derived exosomes from the normal and thin Bactrian camels on hepatocellular carcinoma and their differences at transcriptome and proteomics levels

Yao

Yu²,

Luo³

et al. 2023

Front. Oncol.

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BackgroundHepatocellular carcinoma (HCC) is a common malignant primary tumor. Bactrian camels have high economic and social values, but their potential medical value has not been studied. This study aimed to investigate the effects of Bactrian camel plasma-derived exosomes on HCC.MethodsPlasma was obtained from thin and normal Bactrian camels, and used to isolate exosomes by ultracentrifugation. The exosomes were then characterized by transmission electron microscopy and Nano particle tracking analyzer. In vivo imaging of nude mice and hematoxylin eosin (HE) staining of liver tissues were used to explore the effects of the exosomes on tumor growth. Finally, the differences of the two exosomes were further analyzed using small RNA sequencing and proteomics.ResultsIn vivo imaging and HE staining showed that no significant differences were found in fluorescence value and liver tissue morphology between the control mice and the mice treated with the exosomes from thin Bactrian camels; while the fluorescence value and the live histology changes were alleviated in the mice with the exosomes from normal Bactrian camels. After sequencing and proteomic analysis, 40 differentially expressed miRNAs (DE-miRNAs, 15 down-regulated and 25 up-regulated) and 172 differentially expressed proteins (DEPs, 77 up-regulated and 95 down-regulated) were identified in the plasma-derived exosomes from normal Bactrian camels. These identified DE-miRNAs and DEPs were significantly enriched in many signaling pathways.ConclusionsNormal Bactrian camel plasma-derived exosomes may inhibit the growth of HCC cells through regulating pathways of Ras, Ras-Association Proximate 1 (Rap1), phosphoinositide 3-kinase-protein kinase B (PI3K-Akt), mitogen-activated protein kinase (MAPK), adenosine monophosphate-activated protein kinase (AMPK), and canonical Wnt signaling pathways.

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miR-4454 up-regulated by HPV16 E6/E7 promotes invasion and migration by targeting ABHD2/NUDT21 in cervical cancer

Cited by 16 publications

References 25 publications

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

NUDT21 Promotes Tumor Growth and Metastasis Through Modulating SGPP2 in Human Gastric Cancer

Extracellular vesicle miRNAs in breast milk of obese mothers

Effects of plasma-derived exosomes from the normal and thin Bactrian camels on hepatocellular carcinoma and their differences at transcriptome and proteomics levels

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