miR‑125b regulates the drug‑resistance of breast cancer cells to doxorubicin by targeting HAX‑1

Hu, Guoqing; Zhao, Xiaokang; Wang, Jiang; Lv, Liting; Wang, Chaoqun; Feng, Liang; Shen, Liangqiong; Ren, Weili

doi:10.3892/ol.2017.7476

Cited by 30 publications

(31 citation statements)

References 28 publications

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“…The cytotoxic mechanism of DOX is dependent on apoptotic pathway and involves the inhibition of DNA or RNA synthesis following penetration into DNA. The resistance of breast cancer cells to apoptotic pathways has reduced the clinical effectiveness of this chemotherapeutic drug (49). In the present study, we showed that miR-154 increased the cellular response to DOX and cell survival is significantly decreased when DOX treatment was combined with up-regulation of miR-154.…”

Section: Luciferase Reporter Assay Verifying the Predicted Interactiomentioning

confidence: 47%

“…miR-133b has also been found to be functionally involved in the resistance of breast cancer cells to DOX and the intratumoral delivery of this miRNA increased the treatment response to DOX in DOX-resistant xenografts (51). miR-125b has also been introduces as another regulator of DOX-resistance in breast cancer cells via targeting hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) (46,49). NAMPT overexpression has been shown to be associated with poor treatment response to chemotherapeutic agents including doxorubicin, etoposide, fluorouracil, paclitaxel, and phenylethyl isothiocyanate (52).…”

Section: Luciferase Reporter Assay Verifying the Predicted Interactiomentioning

confidence: 99%

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Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Bolandghamtpour

Nourbakhsh²,

Mousavizadeh

et al. 2019

Preprint

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Background Nicotinamide phosphoribosyltransferase (NAMPT) acts as an important enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) biosynthesis. Deregulation of NAD could be associated with progression of many cancers including breast cancer. Here, we evaluated the effect of NAMPT inhibition via miR-154 on survival of breast cancer cells. Methods Breast cancer cell lines including MCF-7 and MDA-MB-231 were transfected with miR-154 mimic, inhibitor and their negative controls. Using real-time PCR and western blotting techniques the expression levels of NAMPT and miR-154 were determined and compared with the untreated cells. NAD levels were measured by an enzymatic method. Subsequently, colorimetric methods and flow cytometry were performed to evaluate cell viability and apoptosis. Bioinformatics analyses were performed to investigate whether NAMPT 3′-UTR is a direct target of miR-154 and the findings were confirmed by luciferase reporter assay. Results According to the obtained results, NAMPT 3′-UTR was identified as a direct target of miR-154 and the levels of this miRNA was inversely associated with NAMPT expression both at mRNA and protein levels in breast cancer cell lines. Functionally, miR-154 inhibited the NAD salvage pathway leading to a remarkable decrease in cell survival and induction of apoptosis. Co-treatment of breast cancer cells with doxorubicin and miR-154 mimic significantly reduced cell viability compared to treatment with doxorubicin alone in both cell lines. Conclusions Hence, it was concluded that the inhibition of NAD production by miR-154 might be introduced as a promising therapeutic strategy for the treatment of breast cancer either alone or in combination with other conventional chemotherapeutic agents.

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Section: Luciferase Reporter Assay Verifying the Predicted Interactiomentioning

confidence: 47%

Section: Luciferase Reporter Assay Verifying the Predicted Interactiomentioning

confidence: 99%

Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Bolandghamtpour

Nourbakhsh²,

Mousavizadeh

et al. 2019

Preprint

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“…Specifically, various studies have confirmed the expression changes of miR-125b in a variety of cancer tissues and cells. For example, miR-125b as a tumor suppressor gene was downregulated in breast cancer tissues and cells [19], and miR-125b expression in gastric cancer tissues and cells was also significantly downregulated [20]. In this study, it was found that the expression level of miR-125b in GCT tissues and cells was also significantly downregulated.…”

mentioning

confidence: 49%

Fluorescent Mitoxantrone Hydrochloride Nanoparticles Inhibit the Malignant Behavior of Giant Cell Tumor of Bone via miR-125b/PTH1R Axis

Yuan

Zhang

et al. 2020

Journal of Nanomaterials

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Objective. To explore the therapeutic effects and mechanism of fluorescent mitoxantrone hydrochloride nanoparticles on giant cell tumor of bone. Methods. The adsorption capacity of nanoparticles to hydroxyapatite (HA), cell adsorption capacity, encapsulation rate, particle size, and potential of the nanoparticles were determined by HPLC and Zetasizer Nano ZS nanomicelle potentiometer. MTT assay was used to determine the toxicity of nanoparticles to cells. The fluorescent intensity of the nanoparticles and their location in the cells were observed under a fluorescence microscope. RT-qPCR and Western blotting were then used to measure the expression levels of miRNA, mRNA, and proteins in cells. Transwell and Annexin V-FITC/PI staining tests were used to study the cell invasion and apoptotic rate, respectively. The dual-luciferase reporter gene experiment was then carried out to verify the binding relationship between miR-125b and its predicted target. Results. ALN-FOL-MTO-NLC nanoparticles showed a stronger adsorption capacity for HA and stronger toxicity to GCTB28 cells. Compared to normal tissues, the expression level of miR-125b in giant bone tumor tissue and cells was significantly downregulated, and the expression level of miR-125b was upregulated to some extent after treatment. Overexpression of miR-125b or treatment of ALN-FOL-MTO-NLC nanoparticles can inhibit the malignant behavior of GCTB28 cells, whereas the inhibition of the expression of miR-125b can promote the malignant behavior of GCTB28 cells. The result showed that parathyroid hormone receptor 1 (PTH1R) was a downstream target gene for miR-125b. Rescue experiment showed that the treatment of GCTB28 with ALN-FOL-MTO-NLC nanoparticles while inhibiting miR-125b expression can reduce the inhibitory effect of miR-125b on the malignant behavior of GCTB28 cells, whereas upregulating the expression levels of miR-125b and PTH1R in GCTB28 cells had no significant effect on the malignant behavior of GCTB28 cells. Conclusion. ALN-FOL-MTO-NLC nanoparticles have a certain inhibitory effect on the malignant behavior of giant cell tumor of bone through the miR-125b/PTH1R molecular axis.

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“…Studies have reported that overexpression of HAX-1 is usually observed in multiple human cancers. Furthermore, overexpression of HAX-1 has been reported to induce resistance to many chemotherapeutic drugs [32,33]. HAX-1 has become an important target in the chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Restore of miR-541 resensitizes pancreatic cancer cells to gemcitabine-induced apoptosis through suppression of HAX-1

Hong

Gan²,

Zhang

et al. 2020

Preprint

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Background: MiR-541 acts as a tumor suppressor in some cancers. However, the role of miR-541 in regulating the chemosensitivity to cancer cells is still unclear. The aim of this study is to explore the effect of miR-541 on chemoresistance of pancreatic cancer (PCa) cells to gemcitabine-induced apoptosis.Methods: Gemcitabine-resistant Panc-1 and Capan-2 PCa cell lines (Panc-1/R and Capan-2/R) were established through long term exposure to gemcitabine. Effect of miR-541 on changing the sensitivity of Panc-1/R and Capan-2/R to gemcitabine-induced cytotoxicity was evaluated by MTT assays. Regulation of miR-541 on HAX-1 was confirmed by bioinformatics, western blot analysis and luciferase reporter assays. Cell apoptosis and mitochondrial membrane potential (MMP) was measured by flow cytometry analysis.Results: Comparison with Panc-1 and Capan-2, downregulation of miR-541 was observed in Panc-1/R and Capan-2/R cells. Overexpression of miR-541 was found to increase the cytotoxicity of gemcitabine to Panc-1/R and Capan-2/R cells. However, transfection with HAX-1 plasmid can abolish the effect of miR-541 on gemcitabine-induced cytotoxicity against Panc-1/R and Capan-2/R.Conclusion: Downregulation of miR-541 is responsible for development of gemcitabine resistance in PCa. Overexpression of miR-541 may represent a potential strategy to reverse the chemoresistance of PCa.

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miR‑125b regulates the drug‑resistance of breast cancer cells to doxorubicin by targeting HAX‑1

Cited by 30 publications

References 28 publications

Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Down-regulation of NAMPT expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin

Fluorescent Mitoxantrone Hydrochloride Nanoparticles Inhibit the Malignant Behavior of Giant Cell Tumor of Bone via miR-125b/PTH1R Axis

Restore of miR-541 resensitizes pancreatic cancer cells to gemcitabine-induced apoptosis through suppression of HAX-1

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