microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi

Zhao, Zhenze; Partridge, Veronica; Sousares, Michaela; Shelton, Spencer D.; Holland, Cory; Pertsemlidis, Alexander; Du, Lin

doi:10.1371/journal.pone.0208777

Cited by 28 publications

(22 citation statements)

References 40 publications

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“…LINC01234 acts as a ceRNA to modulate CBFB expression in gastric cancer by absorbing miR-204-5p [33]. Herein, we uncovered a ceRNA mechanism of ARAP1-AS1-miR-2110-HDAC2 in BC cells, among which miR-2110 has been identified as an onco-suppressor in in neuroblastoma [34] and HDAC2 is a well-recognized transcriptional co-repressor that plays a carcinogenic role in BC progression [35][36][37]. In our research, miR-2110 overexpression inhibited cell proliferation, migration and stimulated cell apoptosis in BC.…”

Section: Discussionmentioning

confidence: 94%

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Wang

Zhao

et al. 2020

Bioscience Reports

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Breast cancer (BC) poses a great threaten to women health. Numerous evidences suggest the important role of long non-coding RNAs (lncRNAs) in BC development. In the present study, we intended to investigate the role of ARAP1-AS1 in BC progression. First of all, the GEPIA data suggested that ARAP1-AS1 was highly expressed in breast invasive carcinoma (BRAC) tissues compared with the normal breast tissues. Meanwhile, the expression of ARAP1-AS1 was greatly up-regulated in BC cell lines. ARAP1-AS1 knockdown led to repressed proliferation, strengthened apoptosis and blocked migration of BC cells. Moreover, ARAP1-AS1 could boost HDAC2 expression in BC through sponging miR-2110 via a ceRNA mechanism. Of note, the UCSC predicted that HDAC2 was a potential transcriptional regulator of PLIN1, an identified tumor suppressor in BC progression. Moreover, we explained that the repression of HDAC2 on PLIN1 was owing to its deacetylation on PLIN1 promoter. More importantly, depletion of PLIN1 attenuated the mitigation function of ARAP1-AS1 silence on the malignant phenotypes of BC cells. To sum up, ARAP1-AS1 serves a tumor-promoter in BC development through modulating miR-2110/HDAC2/PLIN1 axis, which may help to develop novel effective targets for BC treatment.

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Section: Discussionmentioning

confidence: 94%

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Wang

Zhao

et al. 2020

Bioscience Reports

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“…There are few studies on miR-2110, but it was considered to be a tumor suppressor in neuroblastoma [21] , which may be functioned by directly targeting Tsukushi [26] . Meanwhile, our research also proved that decreased miR-2110 promoted cell proliferation, migration, and invasion in TNBC cells.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple negative breast cancer

Zhang

Zhou

et al. 2020

Preprint

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Background: LncRNAs have been proved to be involved in the proliferation, apoptosis, invasion, migration and other pathological processes of triple negative breast cancer (TNBC). And the expression level of LncRNA AFAP1-AS1 in TNBC was found to be significantly higher than that in other subtypes and normal tissue samples, but the specific mechanism of LncRNA AFAP1-AS1 affecting the occurrence and development of TNBC needs to be revealed.Methods: Cell Counting Kit-8 assays, colony formation assays, wound-healing migration, transwell invasion assays and nude mouse xenograft assays were used to confirm the role of LncRNA AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. Bioinformatics analyses, quantitative polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase assays were performed to confirm the interaction between between LncRNA AFAP1-AS1, miR-2110 and Sp1.Results: In the present study, the silencing of AFAP1-AS1 and Sp1 or the upregulation of miR-2110 would result in the suppression of proliferation, migration and invasion of MDA-MB-231 and MDA-MB-468 cells in vitro as well as tumor growth in vivo. Mechanistically, the dual-luciferase reporter assay highlighted that AFAP1-AS1 functioned as a miR-2110 sponge to increase Sp1 expression. AFAP1-AS1 silencing led to a reduction in Sp1 mRNA and protein levels, which could be reverse by the joint transfection of miR-2110 inhibitor.Conclusions: Our findings demonstrated that AFAP1-AS1 acts as a miR-2110 sponge in TNBC cells, resulting in the regulation of Sp1 expression. And the AFAP1-AS1/miR-2110/Sp1 axis modulated the proliferation, migration and invasion of breast cancer cells and affected the tumorigenesis in mice.

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“…Cell viability and proliferation assays were used to measure the effect of different treatments on cell survival and proliferation. Cell viability was measured by MTT (2-(4, 5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay as previously described [29]. For measuring cell proliferation, 2500 cells were plated and treated in 96-well plates.…”

Section: Cell Viability and Proliferation Assaymentioning

confidence: 99%

“…Colony formation assay was used to measure the longterm effect of treatments on cell proliferation, and it was performed as previously described [29]. Colony numbers and sizes were quantified using Image J (NIH, Bethesda, MD).…”

Section: Colony Formation Assaymentioning

confidence: 99%

“…Cell lysate collection, SDS-PAGE gel electrophoresis, transfer to PVDF membranes, and Western blotting were performed as previously described [29]. For quantitative comparison between treatment groups, the raw band intensities in the Western blot images were quantified using Image J, and the relative band intensities were derived as the following: the raw band intensity of a specific protein in a specific treatment group was first normalized to its corresponding loading control (i.e., calnexin).…”

Section: Western Blotsmentioning

confidence: 99%

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The PLAGL2/MYCN/miR-506-3p interplay regulates neuroblastoma cell fate and associates with neuroblastoma progression

Zhao

Shelton

Oviedo

et al. 2020

J Exp Clin Cancer Res

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Background: The oncogene MYCN is critical for tumorigenesis of several types of cancers including neuroblastoma. We previously reported that miR-506-3p repressed MYCN expression in neuroblastoma cells. However, the mechanism underlying such regulation was undetermined since there is no miR-506-3p target site in MYCN 3'UTR. Methods: By a systematic investigation combining microarray, informatics and luciferase reporter assay, we identified that the transcriptional factor pleiomorphic adenoma gene-like 2 (PLAGL2) is a direct target of miR-506-3p that mediates its regulation on MYCN expression. Using CHIP-PCR and luciferase reporter assay, we validated the transcriptional regulation of MYCN by PLAGL2 and we further demonstrated the transcriptional regulation of PLAGL2 by MYCN. We examined the function of PLAGL2 in regulating neuroblastoma cell fate by cell viability assay, colony formation and Western blotting of differentiation markers. We examined the effect of retinoic acid, the differentiation agent used in neuroblastoma therapy, on miR-506-3p, PLAGL2 and MYCN expressions by quantitative PCR and Western blots. We investigated the clinical relevance of PLAGL2 expression by examining the correlation of tumor PLAGL2 mRNA levels with MYCN mRNA expression and patient survival using public neuroblastoma patient datasets. Results: We found that miR-506-3p directly down-regulated PLAGL2 expression, and we validated a PLAGL2 binding site in the MYCN promoter region responsible for promoting MYCN transcription, thereby establishing a mechanism through which miR-506-3p regulates MYCN expression. Conversely, we discovered that MYCN regulated PLAGL2 transcription through five N-Myc-binding E-boxes in the PLAGL2 promoter region. We further confirmed the reciprocal regulation between endogenous PLAGL2 and MYCN in multiple neuroblastoma cell lines. Moreover, we found that PLAGL2 knockdown induced neuroblastoma cell differentiation and reduced cell proliferation, and combined knockdown of PLAGL2 and MYCN showed a synergistic effect. More strikingly, we found that high tumor PLAGL2 mRNA levels were significantly correlated with high MYCN mRNA levels and poor patient survival in neuroblastoma patients. Furthermore, we found that retinoic acid increased expression of miR-506-3p and repressed expression of MYCN and PLAGL2. Conclusions: Our findings altogether suggest that the interplay network formed by PLAGL2, MYCN and miR-506-3p is an important mechanism in regulating neuroblastoma cell fate, determining neuroblastoma prognosis, and mediating the therapeutic function of retinoic acid.

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microRNA-2110 functions as an onco-suppressor in neuroblastoma by directly targeting Tsukushi

Cited by 28 publications

References 40 publications

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis

Long non-coding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple negative breast cancer

The PLAGL2/MYCN/miR-506-3p interplay regulates neuroblastoma cell fate and associates with neuroblastoma progression

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