A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition

Bai, Jianan; He, Na; Hua, Xiumei; Wei, Yue; Tian, Ye; Zhang, Yiqiang; Guo, Jing; Zeng, Weiwen; Yan, Lijun; Tang, Qiyun

doi:10.18632/oncotarget.14322

Cited by 38 publications

(34 citation statements)

References 27 publications

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“…Our data revealed that miR-224 could negatively regulate PCSK9 expression level by directly targeting its transcript. Our findings are in accordance with former studies that introduced miR-224 as a regulator in lipid metabolism and of PCSK9 in particular (Bai et al 2017 ).…”

Section: Discussionsupporting

confidence: 94%

Post-transcriptional Regulation of PCSK9 by miR-191, miR-222, and miR-224

et al. 2017

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Since proprotein convertase subtilisin kexin 9 (PCSK9) discovery, a gene involved in LDL metabolism regulation and cardiovascular diseases (CVD), many therapeutic strategies have been introduced for direct targeting of PCSK9. The main goal of these strategies has been to reduce PCSK9 protein level either by application of antibodies or inhibition of its production. In this study, we have tried to discover microRNAs (miRNAs) which can target, and hence regulate, PCSK9 expression. Using bioinformatics tools, we selected three microRNAs with binding sites on 3′-UTR of PCSK9. The expression level of these miRNAs was examined in three different cell lines using real-time RT-PCR. We observed a reciprocal expression pattern between expression level of miR-191, miR-222, and miR-224 with that of PCSK9. Accordingly, the expression levels were highest in Huh7 cells which expressed the lowest level of PCSK9, compared to HepG2 and A549 cell lines. PCSK9 mRNA level also showed a significant decline in HepG2 cells transfected with the vectors overexpressing the aforementioned miRNAs. Furthermore, the miRNAs target sites were cloned in psiCHECK-2 vector, and a direct interaction of the miRNAs and the PCSK9 3′-UTR putative target sites was investigated by means of luciferase assay. Our findings revealed that miR-191, miR-222, and miR-224 can directly interact with PCSK9 3′-UTR and regulate its expression. In conclusion, our data introduces a role for miRNAs to regulate PCSK9 expression.

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Section: Discussionsupporting

confidence: 94%

Post-transcriptional Regulation of PCSK9 by miR-191, miR-222, and miR-224

et al. 2017

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“…Moreover, they found that the CRM1 region of TXNIP binds the nuclear transcription factor HIF1α and the ubiquitin ligase pVHL. The TXNIP-pVHL-HIF1α complex results in the degradation of HIF1α [24]. In accordance with these results, our study also showed that TXNIP negatively regulated HIF1α, independently of its interaction with thioredoxin and ROS, as no obvious change in HIF1α mRNA levels was observed.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, our results demonstrated that miR-224 promoted PDAC cell proliferation and migration in vitro, as well as metastasis to the lung in vivo. Thus, miR-224 acts as an oncogene to promote the progression and metastasis of pancreatic cancer, which is consistent with previous studies [13,24]. Although miR-224 is overexpressed in various cancers and promotes cancer progression [25], the mechanism underlying the role of this miRNA in cancer is understood poorly.…”

Section: Discussionsupporting

confidence: 89%

MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway

Zhu

Zhou

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) have been shown to participate in the development of pancreatic ductal adenocarcinoma (PDAC) by modulating multiple cellular processes. Increased miR-224 expression enhances proliferation and metastasis in human cancers. This study aimed to investigate the role of miR-224 and its underlying mechanism of action in PDAC. Methods: BrdU, MTT, and cell migration assays were performed to determine cell proliferation, viability, and migration, respectively. The binding sites of miR-224 were identified using a luciferase reporter system, whereas protein expression of target genes was determined by immunoblotting and immunofluorescence analyses. A BALB/c nude mouse xenograft model was used to evaluate the role of miR-224 in vivo. Results: We demonstrated that miR-224 expression was enhanced in PDAC cells and tissues, and was related to migration and proliferation. Noticeably, miR-224 overexpression promoted the proliferation, migration, and metastasis of Panc1 cells, while miR-224 inhibition had the reverse effect on PDAC cells. Moreover, we found that thioredoxin-interacting protein (TXNIP) is a target of miR-224. The results also indicated that miR-224 inversely regulated TXNIP by binding directly to its 3′-untranslated region, which resulted in the activation of hypoxia-inducible factor 1α (HIF1α). Further, either TXNIP re-expression or HIF1α depletion abolished the effects of miR-224 on the proliferation and migration of PDAC cells in vitro and in vivo. Regarding the relationship of TXNIP and HIF1α, we found that TXNIP mediated the nuclear export of HIF1α and its degradation by forming a complex with HIF1α. Conclusion: The miR-224-TXNIP-HIF1α axis may be useful in developing novel therapies for PDAC.

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“…BON1 cell line was a gift from Dr. He Na, Department of Gastroenterology, the First Affiliated Hospital with Nanjing Medical University (Nanjing, China) [19]. QGP-1 cells were purchased from the Japanese Collection of Research Bioresources Cell Bank (JRCB, Osaka, Japan).…”

Section: Methodsmentioning

confidence: 99%

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

Zhang

Feng

2017

Cell Physiol Biochem

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Background/Aims: Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms which arise from pancreatic islet cells. Recently, lncRNA MEG3 has been reported as a tumor suppressor in variety cancers. This study aimed to reveal the functional effects of MEG3 on pNETs which has not been uncovered previously. Methods: The expression of MEG3, miR-183, and BRI3 in BON1 cells were altered by transfection with their specific vectors/shRNA, or mimic/inhibitor. Thereafter, cell viability, apoptosis, the protein expressions of cell cycle related factors, and apoptosis associated factors, as well as cell migration and invasion were respectively assessed by typan blue staining, flow cytometry, western blotting, and transwell assay. Results: MEG3 was low expressed in BON1 and QGP-1 cells, when compared to three normal cell lines (HEK293, CCL-153, and EC-304). MEG3 overexpression decreased BON1 cells viability, invasion, migration, but significantly induced apoptosis. miR-183 was a direct target of MEG3, and miR-183 up-regulation abolished the anti-growth and anti-metastasis effects of MEG3 overexpression on BON1 cells. Moreover, BRI3 was a target of miR-183, and BRI3 exhibited a tumor-promoting role possibly via activation of p38/ERK/AKT and Wnt/β-Catenin signaling in BON1 cells. Conclusion: This study demonstrated a tumor suppressive effect of MEG3 in BON1 cells that suppresses tumor cells growth and metastasis. A novel regulatory mechanism has been revealed that modulation of MEG3/miR-183/BRI3 axis may be pivotal in pNET.

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A retrospective study of NENs and miR-224 promotes apoptosis of BON-1 cells by targeting PCSK9 inhibition

Cited by 38 publications

References 27 publications

Post-transcriptional Regulation of PCSK9 by miR-191, miR-222, and miR-224

Post-transcriptional Regulation of PCSK9 by miR-191, miR-222, and miR-224

MicroRNA-224 Promotes Pancreatic Cancer Cell Proliferation and Migration by Targeting the TXNIP-Mediated HIF1α Pathway

MEG3 Suppresses Human Pancreatic Neuroendocrine Tumor Cells Growth and Metastasis by Down-Regulation of Mir-183

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