In silico analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors

Bastos, Daniel Rodrigues de; Nagai, María Aparecida

doi:10.1371/journal.pone.0232284

Cited by 21 publications

(13 citation statements)

References 62 publications

(75 reference statements)

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“…Limited knockout of AFAP1-AS1 (about 25–50%) is sufficient to reduce proliferation and colony formation of MDA–MB-231 and HCC1937 cells [ 16 ], meanwhile AFAP1-AS1 knockdown also represses BT-549 and MCF-7 cell proliferation and migration by downregulating septin-2 ( SEPT2 ) via the sponging of miR-497-5p [ 17 ]. An in silico analysis of cDNA microarray data confirmed that AFAP1-AS1 is a potential prognostic factor in TNBC [ 18 ]. In addition, it promotes EMT via the Wnt / β-catenin signaling pathway in TNBC [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Zhou

et al. 2021

Cell Death Dis

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Long noncoding ribonucleic acids (LncRNAs) have been found to be involved in the proliferation, apoptosis, invasion, migration, and other pathological processes of triple-negative breast cancer (TNBC). Expression of the lncRNA actin filament-associated protein 1 antisense RNA1 (AFAP1-AS1) has been found to be significantly higher in TNBC than in other subtypes or in normal tissue samples, but the specific mechanism by which AFAP1-AS1 affects the occurrence and development of TNBC is yet to be revealed. In this study, we used Cell Counting Kit-8 (CCK-8), colony formation, wound healing migration, Transwell invasion, and nude mouse xenograft assays to confirm the role of AFAP1-AS1 in the proliferation, migration of TNBC cells in vitro and in vivo. In addition, we performed bioinformatics analyses, reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), western blot (WB), and dual-luciferase reporter assays (dual-LRA) to confirm interaction among AFAP1-AS1, micro-RNA 2110 (miR-2110), and Sp1 transcription factor (Sp1). We found that silencing AFAP1-AS1 and Sp1 or upregulating miR-2110 suppressed the 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-LRA highlighted that miR-2110 was an inhibitory target of AFAP1-AS1, and 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 reversed by joint transfection with miR-2110 inhibitor. Our findings demonstrated that AFAP1-AS1 could modulate the progression of breast cancer cells and affect tumorigenesis in mice by acting as a miR-2110 sponge, resulting in regulation of Sp1 expression. Therefore, AFAP1-AS1 could play a pivotal role in the treatment of TNBC.

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Section: Introductionmentioning

confidence: 99%

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

Zhang

Zhou

et al. 2021

Cell Death Dis

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“…Emerging studies have reported that various lncRNAs modulates the progression of TNBC, and aberrant expression of lncRNAs worsen the disease (Figure 7) (C. Chen et al, 2015; B. Guo et al, 2020; Le et al, 2019; Naorem et al, 2020; Rodrigues de Bastos & Nagai, 2020). A detailed list of lncRNAs that are associated with TNBC development and progression are mentioned in Table 1, along with their respective mechanisms or outcomes (Table 2) (Ang et al, 2020; Ge et al, 2020).…”

Section: Lncrnas Associated With Tnbcmentioning

confidence: 99%

Long noncoding RNAs in triple‐negative breast cancer: A new frontier in the regulation of tumorigenesis

Thakur

Kumar

Banik

et al. 2021

Journal Cellular Physiology

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In recent years, triple‐negative breast cancer (TNBC) has emerged as the most aggressive subtype of breast cancer and is usually associated with increased mortality worldwide. The severity of TNBC is primarily observed in younger women, with cases ranging from approximately 12%–24% of all breast cancer cases. The existing hormonal therapies offer limited clinical solutions in completely circumventing the TNBC, with chemoresistance and tumor recurrences being the common hurdles in the path of TNBC treatment. Accumulating evidence has correlated the dysregulation of long noncoding RNAs (lncRNAs) with increased cell proliferation, invasion, migration, tumor growth, chemoresistance, and decreased apoptosis in TNBC. Various clinical studies have revealed that aberrant expression of lncRNAs in TNBC tissues is associated with poor prognosis, lower overall survival, and disease‐free survival. Due to these specific characteristics, lncRNAs have emerged as novel diagnostic and prognostic biomarkers for TNBC treatment. However, the underlying mechanism through which lncRNAs perform their actions remains unclear, and extensive research is being carried out to reveal it. Therefore, understanding of mechanisms regulating the modulation of lncRNAs will be a substantial breakthrough in effective treatment therapies for TNBC. This review highlights the association of several lncRNAs in TNBC progression and treatment, along with their possible functions and mechanisms.

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“…Limited knockout of AFAP1-AS1 (about 25-50%) was su cient to reduce the proliferation and colony formation in MDA-MB-231 cells and HCC1937 cells [16] , meanwhile repressed BT-549 and MCF-7 cells proliferation, migration by downregulating SEPT2 via sponging miR-497-5p [17] . An in silico analysis from cDNA microarray data con rmed that AFAP1-AS1 was potential prognostic factor for TNBC patients [18] . And it promoted epithelial-mesenchymal transition by Wnt/β-catenin signaling pathway in TNBC [19] .…”

Section: Introductionmentioning

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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In silico analyses identify lncRNAs: WDFY3-AS2, BDNF-AS and AFAP1-AS1 as potential prognostic factors for patients with triple-negative breast tumors

Cited by 21 publications

References 62 publications

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

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

Long noncoding RNAs in triple‐negative breast cancer: A new frontier in the regulation of tumorigenesis

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

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