MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc

Li, Tao; Wang, Shuling; Jing-Bo, Hao; Zhang, Ying; Hu, Rong; Liu, Xiangqun; Wen-Jie, Cui; Zhou, Linfu

doi:10.1016/j.biopha.2020.109962

Cited by 44 publications

(27 citation statements)

References 32 publications

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“…These findings have highlighted the carcinostatic role of miR-451a in BCa. The carcinostatic role of miR-451a has been substantiated in papillary thyroid carcinoma [17], lung cancer [18] as well as prostate cancer [19]. Likewise, our Fig.…”

Section: Discussionsupporting

confidence: 74%

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

et al. 2020

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Background The downregulation of microRNA (miR)-451a has been reported in bladder cancer (BCa) tissues. Herein, we elucidated the role of miR-451a in BCa with the involvement of DNA methyltransferase 3B (DNMT3B). Methods We first screened the differentially expressed miRNAs from the serum of 12 BCa patients and 10 healthy controls in the BCa database GSE113486. Subsequently, we detected miR-451a expression and CpG island methylation of the promoter in BCa cells T24 and 5637 with DNMT3B knockdown. The downstream mRNAs of miR-451a were predicted by bioinformatics and KEGG enrichment analysis. Afterwards, the expression patterns of DNMT3B, miR-451a and erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EPHA2) were altered in BCa cells to test the ability of cell proliferation, apoptosis, migration as well as invasion. Finally, the effect of miR-451a and DNMT3B was evaluated in vivo. Results miR-451a was significantly reduced in serum of BCa patients and cell lines. Moreover, the expression of DNMT3B in BCa cells was significantly increased, thus promoting methylation of the miR-451a promoter, resulting in miR-451a inhibition. Additionally, we found that miR-451a targeted and negatively regulated EPHA2, while EPHA2 could activate the PI3K/AKT signaling, driving BCa cell growth and metastasis. Conclusions Our study proposed and demonstrated that miR-451a downregulation mediated by DNMT3B is critical for proliferation, migration, and invasion of BCa, which may be beneficial for developing more effective therapies against BCa.

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Section: Discussionsupporting

confidence: 74%

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

et al. 2020

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“…The downregulated miRNAs identi ed in this study also function as tumor suppressors in lung cancer. MiR-144-5p increased the radiosensitivity of NSCLC cells by repressing activating transcription factor 2 (ATF2) [45] and miR-451a decreased doxorubicin resistance in lung cancer via suppressing c-Myc [46]. MiR-144-3p and MiR-30a-3p inhibited the progression of lung cancer via targeting EZH2 and DNA methyltransferase 3a [47,48].…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Transcription Factor-microRNA-mRNA Co-regulatory Networks in Pulmonary Large-cell Neuroendocrine Carcinomas

Cai

Zhang

2020

Preprint

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Background: Large-cell neuroendocrine carcinoma (LCNEC) of the lung is a rare neuroendocrine neoplasm. Previous studies have shown that microRNAs can be widely involved in tumor regulation through targeting critical genes. However, it is unclear about which miRNAs play vital roles in LCNEC’s pathogenesis and how they interact with transcription factors (TFs) to regulate the cancer-related genes. Methods: To clarify the new TFs-miRNA-target gene feed-forward loops (FFLs) model of LCNEC, we integrated multi-omics data from GEO, TRRUST, TRED, and miRTarBase database. First, expression profile datasets for mRNAs (GSE1037) and miRNAs (GSE19945) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. The target genes of the FFL being obtained from the mirTarBase database, the GO and KEGG functional enrichment analysis was performed on the target gene. Then, we screened for key miRNAs in the FFL and perform gene regulatory network analysis based on key miRNAs. Finally, the TF-miRNA-target gene FFLs were constructed by the hypergeometric test.Results: A total of 343 DEGs and 60 DEMs were identified in LCNECs compared to normal tissues, including 210 downregulated, 133 upregulated genes and 29 downregulated, 31 upregulated miRNAs. Additionally, 55 DEMs were predicted through miRanda, mirDB, and TargetScan to be associated with the LCNEC 77 key genes. Finally, ETS1-miR195-CD36 and E2F3-miR195-CD36 from the TF-miRNA-mRNA FFLs were constructed and are significantly enriched in focal adhesion, cytokine-receptor interaction, hematopoietic cell lineage, and transforming growth factor (TGF)-β signaling pathways. Survival analysis showed that the differential expression of the multi-effect factors ETS1, CD36, and hsa-miR-195 in the FFL significantly affected the survival time of LCNEC patients.Conclusion: In summary, we construct the TF-miRNA-target regulatory network, which is helpful to understand the complex LCNEC regulatory mechanisms. The expression difference of regulated multi-effect target factors ETS1, CD36, and hsa-miR-195 has a significant impact on the survival and development of LCNEC.

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“…miR-451a decreases expressions of N-cadherin and Vimentin, whereas it surges expression of E-cadherin. Functional studies show that the direct interaction between miR-451a and c-Myc contributes in blocking EMT and chemoresistance in lung cancer cells (Tao et al, 2020). The well-known oncogenic miRNA miR-21 has a noticeable role in induction of EMT through modulation of the PTEN/Akt/GSK3 beta pathway and regulation of transcription of E-cadherin, vimentin, snail, slug and β-catenin (Dai L. et al, 2019).…”

Section: Emt In Cancermentioning

confidence: 99%

The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition

Hussen

Shoorei

Mohaqiq

et al. 2021

Front. Mol. Biosci.

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Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets.

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MiR-451a attenuates doxorubicin resistance in lung cancer via suppressing epithelialmesenchymal transition (EMT) through targeting c-Myc

Cited by 44 publications

References 32 publications

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

microRNA-451a promoter methylation regulated by DNMT3B expedites bladder cancer development via the EPHA2/PI3K/AKT axis

Identification of Novel Transcription Factor-microRNA-mRNA Co-regulatory Networks in Pulmonary Large-cell Neuroendocrine Carcinomas

The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition

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