LncRNA FOXD3-AS1 promoted chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis

Zeng, Z.; Zhao, Guofang; Zhu, Huarui; Nie, Liangqin; He, Liangmei; Liu, Jiangtao; Li, Rui; Xiao, Shuai; Hua, Gang

doi:10.1186/s12935-020-01402-9

Cited by 27 publications

(23 citation statements)

References 35 publications

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“…LncRNA FOXD3-AS1 has been identified as high expression in a variety of cancers ( 29 , 30 ). In cervical cancer, the expression of FOXD3-AS1 is significantly increased and associated with poor differentiation.…”

Section: Discussionmentioning

confidence: 99%

LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

et al. 2021

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BackgroundLong noncoding RNAs (lncRNAs) can affect the progression of various tumors, including nasopharyngeal carcinoma (NPC). Here, lncRNA FOXD3-AS1 is highly expressed in NPC tissues through bioinformatics analysis and related to the malignant progression of NPC.MethodsBioinformatics analysis and real-time reverse transcription quantitative PCR(RT-qPCR) assay were applied to identify the expression of FOXD3-AS1 in NPC tissues and cells. Specific short hairpin RNAs (shRNAs) or overexpression plasmids were used to knockdown or upregulate FOXD3-AS1 in NPC cells. The effect of FOXD3-AS1 on proliferation and metastasis of NPC was confirmed by CCK8, colony formation, transwell assays in vitro and mouse tumor growth and metastasis models in vivo, of which the mechanism was explored by RNA pull down, mass spectrometry (MS), RNA Immunoprecipitation (RIP), chromatin immunoprecipitation (CHIP) and luciferase assays.ResultsFOXD3-AS1 was highly expressed in NPC tissues and cells. Knockdown of FOXD3-AS1 significantly inhibited proliferation, migration, and invasion of NPC cells in vitro and vivo. FOXD3-AS1 could specifically bind to YBX1 and have a positive effect on the expression of YBX1. Bioinformatics analysis showed that the promoter of YBX1 had a high enrichment of H3K27ac, which promote mRNA transcription and protein translation of YBX1. Moreover, overexpression of YBX1 could reverse the proliferation, migration and invasion arrest caused by FOXD3-AS1 knockdown.ConclusionLncRNA FOXD3-AS1 is highly expressed and promotes malignant phenotype in NPC, which may provide a new molecular mechanism for NPC.

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Section: Discussionmentioning

confidence: 99%

LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

et al. 2021

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“…Recent evidence also indicates that FOXD3-AS1 is closely associated with poor prognosis in patients with NSCLC and plays an oncogenic role. Indeed, FOXD3-AS1 is involved in the pathological cell activities and chemo-resistance of NSCLC by sponging miR-127-3p to modulate MED28 or MDM2 expression, respectively ( 17 , 18 ). However, the role of FOXD3-AS1 in NSCLC remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…In recent studies, FOXD3-AS1 has also been confirmed to play an important role in NSCLC. For instance, FOXD3-AS1 promotes cisplatin chemoresistance of NSCLC cells by directly acting on the miR-127-3p/MDM2 axis ( 17 ). High expression levels of FOXD3-AS1 promote NSCLC progression by regulating the miR-127-3p/mediator complex subunit 28 (MED28) axis ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

et al. 2021

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Long non-coding RNA (lncRNA) is essential to the development and progression of malignant human cancer. Growing evidence suggests that the lncRNA forkhead box D3 antisense 1 (FOXD3-AS1) is a crucial regulatory effector for multiple cancer types and is closely associated with poor prognosis. However, in most cases, the molecular mechanism underlying the role of FOXD3-AS1 in cancer development has not yet been fully elucidated. The present study focused on non-small cell lung cancer (NSCLC) in order to gain insight into how FOXD3-AS1 drives cancer progression. First, FOXD3-AS1 expression in NSCLC tissue samples was detected using reverse transcription-quantitative (RT-qPCR). Moreover, cell proliferation and apoptosis were determined using Cell Counting Kit-8 assays and flow cytometry, respectively. A luciferase reporter assay was then performed to determine whether there was a direct binding association between FOXD3-AS1 and microRNA (miR)-135a-5p. Lastly, a tumor subcutaneous xenograft model was established to examine the role of FOXD3-AS1 in tumor growth. FOXD3-AS1 was significantly overexpressed in NSCLC tissue samples and cell lines compared with normal tissue samples and cells. FOXD3-AS1 silencing expression significantly inhibited A549 and H1229 cell proliferation while inducing apoptosis compared with sh-NC group. The luciferase reporter assay demonstrated the direct binding interaction between FOXD3-AS1 and miR-135a-5p. Moreover, FOXD3-AS1 silencing led to the upregulation of miR-135a-5p in A549 and H1229 cells compared with sh-NC group. It was also demonstrated that miR-135a-5p could bind to the 3′ untranslated region of cyclin-dependent kinase 6 (CDK6) and negatively modulate its transcription. miR-135a-5p knockdown or CDK6 overexpression reversed the inhibition on cell proliferation and apoptosis following FOXD3-AS1 knockdown. Altogether, the present study suggests that FOXD3-AS1 sponges miR-135a-5p to promote cell proliferation and concomitantly inhibit apoptosis by regulating CDK6 expression in NSCLC cells.

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“…Cisplatin can act through lncRNAs that regulate disease progression in lung cancer by sponging miRNAs, whose interaction with lncRNAs modulates a variety of genes in cancer apoptosis, migration, proliferation and resistance [37][38][39][40][41][42]. As the role of lncRNAs in the anticancer effect of monofunctional platinum(II) complexes had not yet been assessed, we used microarray analysis to identify regulated lncRNAs in A549 and IMR90 cells after treatment with cisplatin or phenanthriplatin.…”

Section: Discussionmentioning

confidence: 99%

Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling

Monroe

Moolani

Irihamye

et al. 2021

Preprint

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The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 hours with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and − 4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.

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LncRNA FOXD3-AS1 promoted chemo-resistance of NSCLC cells via directly acting on miR-127-3p/MDM2 axis

Cited by 27 publications

References 35 publications

LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

LncRNA FOXD3-AS1 Promotes the Malignant Progression of Nasopharyngeal Carcinoma Through Enhancing the Transcription of YBX1 by H3K27Ac Modification

lncRNA FOXD3‑AS1 promotes the progression of non‑small cell lung cancer by regulating the miR‑135a‑5p/CDK6 axis

Cisplatin and phenanthriplatin modulate long-noncoding RNA expression in A549 and IMR90 cells revealing regulation of microRNAs, Wnt/β-catenin and TGF-β signaling

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