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MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells.

ABSTRACT: Aim:This study aimed to explore the regulative mechanisms of miR-27a-3p in chemo-resistance of breast cancer cells. Materials and Methods:qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), colony formation assay, and flow cytometry assay. Moreover, luciferase reporter assay was analyzed to verify the downstream target gene of miR-27a-3p. Further investigation in the correlation between miR-27a-3p and BTG2 was launched by WB, flow cytometry assay, and CCK-8 assay. The expression of Akt and p-Akt was detected by WB. Key Findings:Significantly higher miR-27a-3p expression was confirmed in MCF-7/ADR as compared with sensitive cell line MCF-7 (P<0.05). The down-regulation of miR-27a-3p in MCF-7/ADR enhanced the sensitivity of cancer cells to adriamycin treatment, decreased multidrug resistance gene 1/P-glycoprotein (MDR1/P-gp) expression, enhanced the apoptosis-related proteins expression, increased adriamycin-induced apoptosis, and inhibited cell proliferation as compared to NC groups (P<0.05). The up-regulation of miR-27a-3p in MCF-7 showed the opposite results. BTG2 is identified as a direct target of miR-27a-3p and its down-regulation reversed ADR-resistance. BTG2 treatment exhibited inhibitory effect on PI3K/Akt pathway in MCF-7/ADR cells. Significance:miR-27a-3p might be associated with resistance of breast cancer cells to adriamycin treatments, modulating cell proliferation and apoptosis by targeting BTG2 and promoting the PI3K/Akt pathway in breast cancer cells. miR-27a-3p/BTG2 axis might be a potential therapeutic target for clinical BC resistance.

SUBMITTER: Zhu B

PROVIDER: S-EPMC7368588 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells.

Zhu Bei B Chen Weixian W Fu Yue Y Cui Xiaohan X Jin Lei L Chao Jiadeng J Yun Xiao X Gao Peng P Shan Shiting S Li Jun J Yin Xu X Zhu Chunfu C Qin Xihu X

OncoTargets and therapy 20200714

<h4>Aim</h4>This study aimed to explore the regulative mechanisms of miR-27a-3p in chemo-resistance of breast cancer cells.<h4>Materials and methods</h4>qRT-PCR was employed to determine miR-27a-3p expression in two breast cancer cell lines, MCF-7 and MCF-7/adriamycin-resistant cell line (MCF-7/ADR). The two cell lines were treated with miR-27a-3p mimics or inhibitors or corresponding negative control (NC), respectively. The changes were investigated by qRT-PCR, CCK-8 assay, Western blot (WB), c ...[more]

PMID: 32764979

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Project description:BackgroundBone metastasis is a leading cause of morbidity and mortality in advanced prostate cancer (PCa). Downexpression of miR-133a-3p has been found to contribute to the progression, recurrence and distant metastasis in PCa. However, clinical significance of miR-133a-3p in bone metastasis of PCa, and the biological role of miR-133a-3p and its molecular mechanisms underlying bone metastasis of PCa remain unclear.MethodsmiR-133a-3p expression was evaluated in 245 clinical PCa tissues by real-time PCR. Statistical analysis was performed to evaluate the clinical correlation between miR-133a-3p expression and clinicopathological features, and overall and bone metastasis-free survival in PCa patients. The biological roles of miR-133a-3p in the bone metastasis of PCa were investigated both in vitro and in vivo. Bioinformatics analysis, real-time PCR, western blot and luciferase reporter analysis were applied to demonstrate the relationship between miR-133a-3p and its potential targets. Western blotting and luciferase assays were examined to identify the underlying pathway involved in the anti-tumor role of miR-133a-3p. Clinical correlation of miR-133a-3p with its targets was verified in human PCa tissues.ResultsmiR-133a-3p expression is reduced in PCa tissues compared with the adjacent normal tissues and benign prostate lesion tissues, particularly in bone metastatic PCa tissues. Low expression of miR-133a-3p is significantly correlated with advanced clinicopathological characteristics and shorter bone metastasis-free survival in PCa patients by statistical analysis. Moreover, upregulating miR-133a-3p inhibits cancer stem cell-like phenotypes in vitro and in vivo, as well as attenuates anoikis resistance in vitro in PCa cells. Importantly, administration of agomir-133a-3p greatly suppresses the incidence of PCa bone metastasis in vivo. Our results further demonstrate that miR-133a-3p suppresses bone metastasis of PCa via inhibiting PI3K/AKT signaling by directly targeting multiple cytokine receptors, including EGFR, FGFR1, IGF1R and MET. The negative clinical correlation of miR-133a-3p with EGFR, FGFR1, IGF1R, MET and PI3K/AKT signaling activity is determined in clinical PCa tissues.ConclusionOur results unveil a novel mechanism by which miR-133a-3p inhibits bone metastasis of PCa, providing the evidence that miR-133a-3p may serve as a potential bone metastasis marker in PCa, and delivery of agomir-133a-3p may be an effective anti-bone metastasis therapeutic strategy in PCa.

Dataset Information

MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells.

Publications

MicroRNA-27a-3p Reverses Adriamycin Resistance by Targeting BTG2 and Activating PI3K/Akt Pathway in Breast Cancer Cells.

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