miR‐381 overcomes cisplatin resistance in breast cancer by targeting MDR1

Yi, Dandan; Xu, Lei; Wang, Ru; Lu, Xingyi; Sang, Jianfeng

doi:10.1002/cbin.11071

Cited by 45 publications

(28 citation statements)

References 35 publications

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“…38 A recent study reported that miR-381 could overcome CDDP resistance in breast cancer through directly inhibiting MDR1. 20 Correspondingly, our found indicated that miR-381 overexpression overcame CDDP resistance in MCF-7/ CDDP and MDA-MB-231/CDDP cells. Additionally, miR-381 inhibition reversed EZH2 knockdown-mediated enhancement of CDDP sensitivity in MCF-7/CDDP and MDA-MB-231/CDDP.…”

Section: Discussionsupporting

confidence: 58%

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<p>EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression</p>

Dou

Wang

et al. 2019

OTT

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Background: Emerging evidence reveals the vital role of enhancer of zeste homolog 2 (EZH2) in cancer chemoresistance. However, its function and molecular mechanisms in breast cancer chemoresistance remain largely unknown. Methods: Gene expression was evaluated using quantitative real-time PCR (qRT-PCR) and Western blot analysis. The functional roles of EZH2 and miR-381 in breast cancer were explored using cell MTT assay and flow cytometry analysis. The effect of EZH2 on miR-381 expression in transcriptional level was determined using Chromatin immunoprecipitation (ChIP) assay and Luciferase reporter assay. Results: In this study, we found that EZH2 was up-regulated in CDDP-resistant breast cancer tissues and cell lines. Breast cancer patients with high EZH2 expression had a poor prognosis. EZH2 silencing improved the sensitivity of MCF-7/CDDP and MDA-MB-231/ CDDP cells towards CDDP. Moreover, EZH2 could epigenetically silence miR-381. miR-381 overexpression could overcome CDDP resistance in CDDP-resistant breast cancer cells. miR-381 knockdown weakened the inductive effect of EZH2 silencing on CDDP sensitivity of MCF-7/CDDP and MDA-MB-231/CDDP cells. Furthermore, EZH2 knockdown facilitated CDDP sensitivity of CDDP-resistant breast cancer cells in vivo. Conclusions: Collectively, EZH2 depletion overcame CDDP resistance of breast cancer through epigenetically silencing miR-381, providing a novel therapeutic target for breast cancer chemoresistance.

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Section: Discussionsupporting

confidence: 58%

“…19 Recently, miR-381 was reported to overcome CDDP sensitivity in breast cancer through targeting MDR1. 20 All these studies suggested that miR-381 was closely implicated with cancer chemoresistance. However, how miR-381 was regulated in breast cancer is still largely unknown.…”

Section: Introductionmentioning

confidence: 99%

<p>EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression</p>

Dou

Wang

et al. 2019

OTT

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“…Similar trends have also been previously in miR-124-3p [22] and miR-203a [23]. As for miR-381, it has been particularly suggested to play critical functions in overcoming cisplatin resistance in breast cancer treatment [24][25][26].…”

Section: Discussionsupporting

confidence: 79%

MicroRNA-381 inhibits bladder cancer pathogenesis through directly controlling BMI1 and triggering the Rho/ROCK signaling pathway defect

Chen

Liu

Cao

et al. 2020

Preprint

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Background Emerging evidence has noted the important participation of microRNAs (miRNAs) in several human diseases including cancer control. This research was launched to probe the function of miR-381 in bladder cancer (BCs) progression. Methods Aberrantly expressed miRNAs in BCs tissues were analyzed using miRNA microarrays. miR-381 expression in the bladder and paired tumor tissues, and in BCs and normal cell lines was determined. The target relationship between miR-381 and BMI1 was predicted online and validated through a luciferase assay. Gain-of-functions of miR-381 and BMI1 were performed to identify their functions on BCs cell behaviors as well as tumor growth in vivo. Results miR-381 was poor regulated in BCs tissues and cells. A higher miR-381 level indicates a better prognosis of patients with BCs. Artificial up-regulation of miR-381 inhibited proliferation, invasion, migration, resistance to apoptosis, and tumor formation ability of BCs cells. miR-381 directly binds to BMI1 expression. Overexpression of BMI1 partially blocked the tumor suppressing roles of miR-381 in cell malignancy and tumor growth. In addition, miR-381 led to decreased RhoA phosphorylation and ROCK2 activation, which were also reversed by BMI1. Conclusion The study evidenced that miR-381 may act as a beneficiary biomarker in BCs patients. Up-regulation of miR-381 could suppress BCs development both in vivo and in vitro through BMI1 down-regulation and the Rho/ROCK inactivation.

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“…In addition, recent studies have shown that miR-381 has a very important role in tumor oncogenesis, development, metastasis and chemical resistance. For example, miR-381 inhibits the proliferation and invasion of prostate cancer cells via the regulation of UBE2C [41]; miR-381 inhibits lung adenocarcinoma progression by directly targeting LMO3 through the regulation of the PI3K/Akt signaling pathway and EMT [42]; up-regulation of miR-381 inhibits the NAD + salvage pathway and promotes apoptosis in breast cancer cells [43]; miR-381 overcomes cisplatin resistance in breast cancer cells by targeting MDR1 [44]. In line with these findings, metformin upregulated the level of miR-381 to inhibit NSCLC tumor growth and metastasis in our study.…”

Section: Discussionmentioning

confidence: 99%

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

Jin

Guo

et al. 2020

J Exp Clin Cancer Res

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Background: Recent evidence indicates that metformin inhibits mammalian cancer growth and metastasis through the regulation of microRNAs. Metformin regulates miR-381 stability, which plays a vital role in tumor progression. Moreover, increased YAP expression and activity induce non-small cell lung cancer (NSCLC) tumor growth and metastasis. However, the molecular mechanism underpinning how metformin-induced upregulation of miR-381 directly targets YAP or its interactions with the epithelial-mesenchymal transition (EMT) marker protein Snail in NSCLC is still unknown. Methods: Levels of RNA and protein were analyzed using qPCR, western blotting and immunofluorescence staining. Cellular proliferation was detected using a CCK8 assay. Cell migration and invasion were analyzed using wound healing and transwell assays. Promoter activity and transcription were investigated using the luciferase reporter assay. Chromatin immunoprecipitation was used to detect the binding of YAP to the promoter of Snail. The interaction between miR-381 and the 3′UTR of YAP mRNA was analyzed using the MS2 expression system and co-immunoprecipitation with biotin. Results: We observed that miR-381 expression is negatively correlated with YAP expression and plays an opposite role to YAP in the regulation of cellular proliferation, invasion, migration, and EMT of NSCLC cells. The miR-381 function as a tumor suppressor was significantly downregulated in lung cancer tissue specimens and cell lines, which decreased the expression of its direct target YAP. In addition, metformin decreased cell growth, migration, invasion, and EMT via up-regulation of miR-381. Moreover, YAP, which functions as a co-transcription factor, enhanced NSCLC progression and metastasis by upregulation of Snail. Snail knockdown downregulated the mesenchymal marker vimentin and upregulated the epithelial marker E-cadherin in lung cancer cells. Furthermore, miR-381, YAP, and Snail constitute the miR-381-YAP-Snail signal axis, which is repressed by metformin, and enhances cancer cell invasiveness by directly regulating EMT. Conclusions: Metformin-induced repression of miR-381-YAP-Snail axis activity disrupts NSCLC growth and metastasis. Thus, we believe that the miR-381-YAP-Snail signal axis may be a suitable diagnostic marker and a potential therapeutic target for lung cancer.

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miR‐381 overcomes cisplatin resistance in breast cancer by targeting MDR1

Cited by 45 publications

References 35 publications

<p>EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression</p>

<p>EZH2 Contributes To Cisplatin Resistance In Breast Cancer By Epigenetically Suppressing miR-381 Expression</p>

MicroRNA-381 inhibits bladder cancer pathogenesis through directly controlling BMI1 and triggering the Rho/ROCK signaling pathway defect

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis

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