MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1

Zhang, Qiang; Yuan, Yonghui; Cui, Jianchun; Xiao, Tingting; Jiang, Daqing

doi:10.7150/jca.10822

Cited by 39 publications

(41 citation statements)

References 30 publications

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“…miR-217 was also shown to act as a tumor suppressor in pancreatic ductal adenocarcinoma (57), lung cancer (58), osteosarcoma (59), and esophageal squamous cell carcinoma (60), and accordingly its expression level is reduced in these tumors. In contrast, miR-217 was found to be overexpressed in breast cancer and to enhance tumor proliferation via promoting cell cycle progression (61). Based on the findings reported in this work, it is reasonable to assume that the aberrant expression of miR-200 family members and miR-217 in cancer is also affecting sensitivity of those cancer cells to CDC, but this remains to be determined.…”

Section: Discussionmentioning

confidence: 43%

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

Hillman

Mazkereth

Farberov

et al. 2016

The Journal of Immunology

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The impact of microRNAs (miRNAs) known to regulate numerous biologic processes on complement-dependent cytotoxicity (CDC) was investigated in K562 cells. The C5b-9 complex is the executioner of CDC. Cells protect themselves from CDC by C5b-9 elimination, a process involving the mitochondrial chaperone mortalin/GRP75. Potential miR-200 (b and c) and miR-217 regulatory sites were identified in mortalin mRNA. Overexpression of miR-200b/c or miR-217 lowered the expression of mortalin mRNA. miRNA inhibitors for miR-200b, miR-200c, or miR-217 enhanced mortalin mRNA level. Unexpectedly, these miRNA modulators had no significant effect on mortalin protein level. Metabolic labeling analysis demonstrated that, to compensate for reduction in mortalin mRNA level, the cells increased the rate of synthesis of mortalin protein. Cells overexpressing miR-200b/c or miR-217 showed reduced sensitivity to CDC, whereas inhibition of miR-200c and miR-217 enhanced cell death. miR-200b/c overexpression reduced C5b-9 binding and enhanced its release from the cells and promoted mortalin relocation to the plasma membrane. Inhibition of miR-200 (b and c) and miR-217 had no effect on the expression level of the membrane complement-regulatory proteins CD46, CD55, and CD59. However, overexpression of miR-200b/c or miR-217 enhanced expression of CD46 and CD55 (not of CD59). Overall, the data demonstrate miRNA regulation of cell sensitivity to CDC. We identified miR-200b, miR-200c, and miR-217 as regulators of mortalin and, perhaps indirectly, of CD46 and CD55. Cell exposure to a sublytic dose of complement was shown to increase expression of miR-200 (b and c), suggesting that complement C5b-9 exerts a feedback-regulatory effect on these miRNAs.

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Section: Discussionmentioning

confidence: 43%

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

Hillman

Mazkereth

Farberov

et al. 2016

The Journal of Immunology

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“…MiR-217 is overexpressed in breast cancer tissues, and promotes cell growth by targeting DACH1 [8]. Song et al [9] reported that miR-211, an miRNA that is suppressed in breast cancer, acts as a modulator of cell growth and migration by negatively regulating the expression of CDC25B in breast cancer cell lines.…”

Section: Introductionmentioning

confidence: 98%

“…As in other cancers, cells undergo genetic and epigenetic changes during the progressive stages of breast cancer. Accumulating evidence shows that altered miRNAs can indeed participate in the regulation of cell growth, apoptosis, migration, and invasion in breast cancer [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2

Ren

Shi

et al. 2017

Anti-Cancer Drugs

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MicroRNAs (miRNAs) contribute toward tumorigenesis through the modulation of tumor-related genes. MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. However, the functional role of miR-148a in breast cancer is not yet fully understood. Using both in-vitro and in-vivo models, we confirmed that miR-148a acts to inhibit the proliferation of breast cancer cells. Through the use of bioinformatic approaches in miRNA target prediction, we determined that B-cell lymphoma 2 (BCL-2) is a likely target of miR-148a. The overexpression and tumorigenic effects of BCL-2 have already been confirmed in cancerous tumors of the breast. A dual-luciferase assay was performed to confirm that miR-148a targets the 3'-untranslated region of BCL-2. In this study, we first characterized the downregulation of miR-148a in breast cancer tissues. We then found that restoring expression of miR-148a suppressed the expression of BCL-2 at the level of both mRNA and protein. Upregulation of miR-148a caused a subsequent reduction of proliferation and an increase in apoptosis. In conclusion, we have confirmed the role of miR-148a as a pivotal regulator in breast cancer through its targeting of BCL-2. This evidence strongly suggests that miR-148a could prove to be a novel therapeutic target in breast cancer.

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“…These studies indicate that miR-217 mainly functions as a tumor suppressor in several types of cancer. However, miR-217 also functions as an oncogene in human breast cancer by targeting the Dachshund homolog 1 to enhance cell proliferation (29). These ambivalent results suggest that the functions of miR-217 in cancers are tissue-type dependent.…”

Section: Discussionmentioning

confidence: 60%

“…However, in breast cancer, miR-217 was upregulated in tumor tissues in comparison with normal breast tissues. High levels of miR-217 were significantly associated with high histological grade, the triple negative subtype and advanced tumor stage (29). These conflicting studies indicate that miR expression levels vary in different types of tumor, and that is has tissue specificity.…”

Section: Discussionmentioning

confidence: 86%

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

Xiao

Deng

et al. 2017

Oncology Letters

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Abstract. Acute myeloid leukemia (AML) is a heterogeneous malignant disorder derived from the myeloid hematopoietic cells that accounts for ~80% of all adult acute leukemia. Numerous studies have shown that drug resistance not only exists against conventional chemotherapeutic drugs, but also limits the efficacy of new biological agents. Therefore, it is important to identify the mechanisms behind chemoresistance and seek therapeutic strategies to enhance efficacy in AML chemotherapy. MicroRNA (miR)-217 has been recognized as a tumor suppressor that is downregulated in various types of cancer, however the mechanisms behind the expression and function of miR-217 in AML have not yet been recognized. The expression of miR-217 was determined by quantitative polymerase chain reaction (qPCR). Following transfection with miR-217 mimics, an MTT assay, chemosensitivity assay, cell apoptosis assay and western blot analysis were performed in AML cell lines. Functional assays were also performed to explore the effects of endogenous Kirsten rat sarcoma viral oncogene homolog (KRAS) in AML. The results revealed that miR-217 was downregulated in patients with AML. Overexpression of miR-217 inhibited cellular proliferation and enhanced cell chemosensitivity to doxorubicin by the cell apoptosis pathway in AML cells. A dual-luciferase reporter assay demonstrated that KRAS was a direct target gene of miR-217 in vitro. qPCR and western blot analysis revealed that miR-217 negatively regulated KRAS protein expression, but had no impact on KRAS mRNA expression. Knockdown of KRAS expression markedly suppressed AML cellular proliferation, and enhanced cell chemosensitivity to doxorubicin via the cell apoptosis pathway. These findings indicate that miR-217 functions as a tumor suppressor in AML by directly targeting KRAS. Therefore, miR-217-based therapeutic strategies may provide a novel strategy for the enhancement of efficacy in the treatment of AML.

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MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1

Cited by 39 publications

References 30 publications

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

Regulation of Complement-Dependent Cytotoxicity by MicroRNAs miR-200b, miR-200c, and miR-217

MicroRNA-148a promotes apoptosis and suppresses growth of breast cancer cells by targeting B-cell lymphoma 2

MicroRNA 217 inhibits cell proliferation and enhances chemosensitivity to doxorubicin in acute myeloid leukemia by targeting KRAS

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