miR‐200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer

Tang, Hailin; Song, Cailu; Ye, Feng; Gao, Guanfeng; Ou, Xueqi; Zhang, Lijuan; Xie, Xiaoming

doi:10.1111/jcmm.14681

Cited by 27 publications

(21 citation statements)

References 52 publications

(88 reference statements)

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“…In addition, the inhibition of breast cell migration and invasion by trastuzumab was enhanced by miR-135b-5p agomir transfection. Tang et al (31) indicated that overexpression of miR-200c increased drug sensitivity to trastuzumab in HER-2-positive breast cancer cells, consistent with the data reported here. miR-135b-5p agomir enhanced the antitumor effect of trastuzumab in vivo and in vitro.…”

Section: Discussionsupporting

confidence: 91%

miR‑135b‑5p enhances the sensitivity of HER‑2 positive breast cancer to trastuzumab via binding to cyclin�D2

Qin

Chen

et al. 2020

Int J Mol Med

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Trastuzumab has led to a marked improvement in the outcomes of patients with human epidermal growth factor receptor 2 (HER-2)-positive breast cancer. However, the effects of trastuzumab on HER-2-positive breast cancer are limited by the emergence of its cardiotoxicside effects. MicroRNA (miR)-135b-5p has been shown to inhibit tumor metastasis in breast cancer. The present study aimed to explore the effects of miR-135b-5p overexpression on the efficacy of trastuzumab in HER-2-positive breast cancer. Reverse transcription-quantitative PcR was performed to detect the levels of miR-135b-5p. cell viability was evaluated with a cell counting Kit-8 assay. Annexin V/propidium iodide staining was employed to detect the number of apoptotic cells. Flow cytometry assay was performed to investigate the cell cycle. Western blotting was used to detect the expression levels of Bax, cleaved caspase-3, Bcl-2, cyclin d2, p27 Kip1 and cyclin E1. cell migration and invasion were detected by Transwell assay. Luciferase assays were conducted to identify the target gene of miR-135b-5p. In addition, an in vivo tumor xenograft model was established. miR-135b-5p agomir significantly enhanced the anti-proliferative effect of trastuzumab on HER-2-positive breast cancer cells via the induction of apoptosis, whereas the anti-metastatic effect of trastuzumab was enhanced by miR-135b-5p agomir treatment. Subsequently, luciferase assays indicated that cyclin d2 was the direct target of miR-135b-5p, whereas overexpression of the latter arrested cell cycleduring the G 0 /G 1 phase. Moreover, miR-135b-5p agomir notably increased the antitumor effect of trastuzumab in vivo. The data demonstrated that miR-135b-5p sensitized HER-2-positive breast cancer cells to trastuzumab in vitro and in vivo by directly binding to cyclin d2. These results suggested that the combination of miR-135b-5p with trastuzumab may be a therapeutic strategy for patients with HER-2-positive breast cancer.

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Section: Discussionsupporting

confidence: 91%

miR‑135b‑5p enhances the sensitivity of HER‑2 positive breast cancer to trastuzumab via binding to cyclin�D2

Qin

Chen

et al. 2020

Int J Mol Med

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“…35 CD24, a sialoglycoprotein cell adhesion molecule that promotes adhesion and metastasis, was up-regulated in colon cancer patients with higher ST6GAL1 levels 36 and modulated chemosensitivity of breast cancer cells to 5-fluorouracil. 37 CD44 + CD24 − is a well-known surface marker for breast cancer stem cells responsible for tumor formation, infinite growth, recurrence, and metastasis, 38 suggesting an important role of CD24 in the breast cancer metastasis, chemosensitivity, and stemness.…”

Section: Discussionmentioning

confidence: 99%

<p>ST6GAL2 Downregulation Inhibits Cell Adhesion and Invasion and is Associated with Improved Patient Survival in Breast Cancer</p>

Cheng¹,

Wang²,

Zhong³

et al. 2020

OTT

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These authors contributed equally to this workObjective: Breast cancer is one of the most common and serious types of cancer, with a particularly unfavorable prognosis. Although dysregulation of β-galactoside α 2,6-sialyltransferase 2 (ST6GAL2) has been observed in multiple cancers, the mechanism involved remains to be clarified. In this study, we focused on the potential function of ST6GAL2 in the regulation of breast cancer. Methods: Flow cytometry and CCK-8 were used to measure markers of the cell cycle proliferation, adhesion, and invasion. Real-time PCR and immunohistochemistry analysis were used to detect the expression levels of ST6GAL2 in breast cancer tissues. Western blot was used to analyze the expression level of genes correlated with focal adhesion and metastasis pathways in breast cancer cells. Results: ST6GAL2 expression levels were higher in breast cancer tissues as compared to healthy tissues. ST6GAL2 expression was associated with tumor stage, survival time, and estrogen receptor (ER)/progesterone receptor (PR)/human epidermal growth factor receptor 2 (HER2) status of breast cancer patients. Silence of ST6GAL2 inhibited cancer progression by arresting cell cycle progression at G0/G1 phase and inhibiting cell adhesion and invasion. ST6GAL2 was positively correlated with focal adhesion and metastasis pathways, and its downregulation inhibited the expression of ICAM-1, VCAM-1, CD24, MMP2, MMP9, and CXCR4. Conclusion: These findings indicated that ST6GAL2 might serve as a useful potential target for treatment of breast cancer.

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“…The miR-200 family serves as tumor suppressors in a wide range of diseases and tumor entities, including breast cancer [ 32 , 52 ]. Numerous studies reported relevant roles for miR-200b and miR-200c in the inhibition of breast cancer initiation and progression of cancer via suppression of pivotal oncogenic functions and mechanisms, namely the EMT program, metastasis, cancer stem cell phenotype, and chemoresistance [ 52 , 53 , 54 , 55 , 56 , 57 ]. Apart from the tumor-suppressive role of the miR-200 family, other studies proposed that overexpression of miR-200s promotes the proliferative potential and metastatic capacity of transformed mammary epithelial cells [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

et al. 2020

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Inflammatory breast cancer (IBC) is a rare yet aggressive breast cancer variant, associated with a poor prognosis. The major challenge for IBC is misdiagnosis due to the lack of molecular biomarkers. We profiled dysregulated expression of microRNAs (miRNAs) in primary samples of IBC and non-IBC tumors using human breast cancer miRNA PCR array. We discovered that 28 miRNAs were dysregulated (10 were upregulated, while 18 were underexpressed) in IBC vs. non-IBC tumors. We identified 128 hub genes, which are putative targets of the differentially expressed miRNAs and modulate important cancer biological processes. Furthermore, our qPCR analysis independently verified a significantly upregulated expression of miR-181b-5p, whereas a significant downregulation of miR-200b-3p, miR-200c-3p, and miR-203a-3p was detected in IBC tumors. Receiver operating characteristic (ROC) curves implied that the four miRNAs individually had a diagnostic accuracy in discriminating patients with IBC from non-IBC and that miR-203a-3p had the highest diagnostic value with an AUC of 0.821. Interestingly, a combination of miR-181b-5p, miR-200b-3p, and miR-200c-3p robustly improved the diagnostic accuracy, with an area under the curve (AUC) of 0.897. Intriguingly, qPCR revealed that the expression of zinc finger E box-binding homeobox 2 (ZEB2) mRNA, the putative target of miR-200b-3p, miR-200c-3p, and miR-203a-3p, was upregulated in IBC tumors. Overall, this study identified a set of miRNAs serving as potential biomarkers with diagnostic relevance for IBC.

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miR‐200c suppresses stemness and increases cellular sensitivity to trastuzumab in HER2+ breast cancer

Cited by 27 publications

References 52 publications

miR‑135b‑5p enhances the sensitivity of HER‑2 positive breast cancer to trastuzumab via binding to cyclin�D2

miR‑135b‑5p enhances the sensitivity of HER‑2 positive breast cancer to trastuzumab via binding to cyclin�D2

<p>ST6GAL2 Downregulation Inhibits Cell Adhesion and Invasion and is Associated with Improved Patient Survival in Breast Cancer</p>

Inflammatory Breast Carcinoma: Elevated microRNA miR-181b-5p and Reduced miR-200b-3p, miR-200c-3p, and miR-203a-3p Expression as Potential Biomarkers with Diagnostic Value

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