MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down-regulating the expression of MCL-1

Xie, Qing; Wang, Shuai; Zhao, Yue; Zhang, Zhenchao; Qin, Chuan; Yang, Xinyue

doi:10.18632/oncotarget.15781

Cited by 57 publications

(40 citation statements)

References 36 publications

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“…NDRG2 was introduced into SW620 cells, after which the cell cycle arrest was observed to arrest at G1/S phase [37] Cisplatin is the most common platinum-based chemotherapy drug. Its action mechanism is DNA crosslinking, so its tumor-suppressive activity is broad-spectrum and non-cell cycle-specific, leading to the inhibition of DNA replication and transcription and induction of tumor cell apoptosis [42,43]. Although cisplatin has been considered an effective agent for ovarian cancer treatment, the acquisition and development of drug resistance has emerged as a primary obstacle to its wide clinical application [44].…”

Section: Discussionmentioning

confidence: 99%

NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

Kang

Wang

Luo

et al. 2020

Preprint

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Background: The cancer cell metastasis and the acquisition of chemotherapy resistance remain huge challenge for ovarian cancer treatment. Previously, N-myc downstream-regulated gene 2 (NDRG2) serves as a tumor suppressor for many cancers. Here, we attempted to investigate the specific roles of NDRG2 in ovarian cancer. Methods: The expression levels of NDRG2 were detected by qRT-PCR or Immunoblotting. CCK-8 assay was employed to examine the cell viability of ovarian cancer cells. The colony formation ability was determined by colony formation assay. Flow cytometry analyses were performed to detect the cell apoptosis and cell cycle. Xenograft tumor assay was performed to detect the in vivo function of NDRG2. Results: We revealed that NDRG2 mRNA expression and protein levels were downregulated within both ovarian cancer tissues and cell lines. The overexpression of NDRG2 dramatically inhibited the cell viability and colony formation and tumor growth, whereas promoted the cell apoptosis, cell cycle arrest in G1 phase within ovarian cancer cells. More importantly, NDRG2 overexpression significantly enhanced the suppressive roles of cisplatin (DDP) in ovarian cancer cell viability. On the contrary, NDRG2 silence exerted opposing effects on ovarian cancer cells. Conclusions: In summary, we provide a solid experimental basis demonstrating the tumor-suppressive effects of NDRG2 in inhibiting the cell proliferation, enhancing the cell apoptosis, eliciting the cell cycle arrest in G1 phase, and promoting the suppressive effects of DDP on the viability of ovarian cancer cells. NDRG2 administration presents a potent adjuvant treatment for ovarian cancer therapy.

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Section: Discussionmentioning

confidence: 99%

NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

Kang

Wang

Luo

et al. 2020

Preprint

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“…Among these proteins, we observed that the expression of MCL-1, which is an anti-apoptotic Bcl-2 family protein [26], was clearly increased in γδ T cell-resistant CD133 + A549 and PC9 cells (Fig. 3B).…”

Section: Imperatorin Sensitizes Cd133 + Lung Cancer Cells To γδ T Celmentioning

confidence: 95%

Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to γδ-T Cell-Mediated Cytotoxicity

You

Gao

2018

Cell Physiol Biochem

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Background/Aims: CD133⁺ cancer cells display low sensitivity to anti-cancer treatment; thus, combination treatment with adjuvant drugs is required to improve the efficiency of cancer therapy. The aim of this study was to explore the effect of imperatorin, a linear furanocoumarin compound, on γδ T cell-mediated cytotoxicity against CD133⁺ lung cancer cells. Methods: CD133⁺ and CD133^- subgroups from A549 and PC9 lung cancer cells were sorted by using flow cytometry. The cytotoxicity of γδ T cells against cancer cells was evaluated by measuring lactate dehydrogenase release. The concentration of tumor necrosis factor-related apoptosis-inducing ligand in the co-culture system was determined by using an enzyme-linked immunosorbent assay. Mitochondrial membrane potential, expression of death receptor 4 (DR4) and DR5 on the cell surface, and rate of apoptosis were measured by flow cytometry. Cytochrome c release and cellular protein expression were detected by western blot analysis. Results: Compared with CD133^- cells, CD133⁺ cells were resistant to γδ T cell-mediated cytotoxicity. However, imperatorin significantly increased the sensitivity of CD133⁺ lung cancer cells to γδ T cell treatment in vitro and in vivo. Mechanically, we found that myeloid cell leukemia 1 (MCL-1), an important anti-apoptotic protein belonging to the Bcl-2 family, was overexpressed in CD133⁺ A549 and PC9 cells compared to their corresponding CD133^- cells. Co-treatment with imperatorin and γδ T cells suppressed the expression of MCL-1, and thus promoted the mitochondrial apoptosis mediated by γδ T cells in CD133⁺ A549 and PC9 lung cancer cells. Conclusion: Up-regulated MCL-1 in CD133⁺ lung cancer cells is responsible for their resistance to γδ T cells. Furthermore, the combination of γδ T cells with imperatorin sensitized CD133⁺ lung cancer cells to γδ T cell-mediated cytotoxicity by targeting MCL-1.

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“…Recently, reduced expression of miR-519d was detected in BCSCs, and induced upregulated expression of miR-519d in cancer stem cells has been shown to sensitize towards chemotherapeutic drug cisplatin through activation of the mitochondrial apoptotic pathway. As a result, this significantly increased their sensitivity to cisplatin through MCL-1, a member of the proapoptotic Bcl-2 family, a dependent mitochondrial pathway in BCSCs [90].…”

Section: Breast Cancermentioning

confidence: 99%

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

Khan

Ahmed

Elareer

et al. 2019

Cells

239

168

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Recent biomedical discoveries have revolutionized the concept and understanding of carcinogenesis, a complex and multistep phenomenon which involves accretion of genetic, epigenetic, biochemical, and histological changes, with special reference to MicroRNAs (miRNAs) and cancer stem cells (CSCs). miRNAs are small noncoding molecules known to regulate expression of more than 60% of the human genes, and their aberrant expression has been associated with the pathogenesis of human cancers and the regulation of stemness features of CSCs. CSCs are the small population of cells present in human malignancies well-known for cancer resistance, relapse, tumorigenesis, and poor clinical outcome which compels the development of novel and effective therapeutic protocols for better clinical outcome. Interestingly, the role of miRNAs in maintaining and regulating the functioning of CSCs through targeting various oncogenic signaling pathways, such as Notch, wingless (WNT)/β-Catenin, janus kinases/ signal transducer and activator of transcription (JAK/STAT), phosphatidylinositol 3-kinase/ protein kinase B (PI3/AKT), and nuclear factor kappa-light-chain-enhancer of activated B (NF-kB), is critical and poses a huge challenge to cancer treatment. Based on recent findings, here, we have documented the regulatory action or the underlying mechanisms of how miRNAs affect the signaling pathways attributed to stemness features of CSCs, such as self-renewal, differentiation, epithelial to mesenchymal transition (EMT), metastasis, resistance and recurrence etc., associated with the pathogenesis of various types of human malignancies including colorectal cancer, lung cancer, breast cancer, head and neck cancer, prostate cancer, liver cancer, etc. We also shed light on the fact that the targeted attenuation of deregulated functioning of miRNA related to stemness in human carcinogenesis could be a viable approach for cancer treatment.

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MiR-519d impedes cisplatin-resistance in breast cancer stem cells by down-regulating the expression of MCL-1

Cited by 57 publications

References 36 publications

NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

NDRG2 gene expression pattern in ovarian cancer and its specific roles in inhibiting cancer cell proliferation and suppressing cancer cell apoptosis

Imperatorin Targets MCL-1 to Sensitize CD133+ Lung Cancer Cells to γδ-T Cell-Mediated Cytotoxicity

Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies

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