Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer

Gu, Yu; Chen, Tianxiang; Li, Guangliang; Xu, Cong; Xu, Zhenzhen; Zhang, Jing; He, Kuifeng; Zheng, Linyan; Guan, Zhonghai; Su, Xiu; Cao, Jiashu; Teng, Lisong

doi:10.18632/oncotarget.11044

Cited by 38 publications

(23 citation statements)

References 70 publications

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“…Given the oncogenic function of ErbB2 in acquired tamoxifen resistance, miR-34a expression may be a prognostic target to predict tamoxifen responsiveness in ER + breast cancer patients. In addition, the knockdown of Beclin1, a target of miR-221 [ 19 ], has been reported to suppress ErbB2 expression and restore tamoxifen sensitivity in resistant MCF-7 cells in vitro [ 98 ]. Consistently, clinical data from ER + breast cancer patients taking tamoxifen have demonstrated that high Beclin1 expression is correlated with decreased patient survival [ 98 ].…”

Section: Mirnas and Drug Resistancementioning

confidence: 99%

“…In addition, the knockdown of Beclin1, a target of miR-221 [ 19 ], has been reported to suppress ErbB2 expression and restore tamoxifen sensitivity in resistant MCF-7 cells in vitro [ 98 ]. Consistently, clinical data from ER + breast cancer patients taking tamoxifen have demonstrated that high Beclin1 expression is correlated with decreased patient survival [ 98 ]. Based on reports highlighting the oncogenic role of Beclin1 in ER + breast cancer, miR-221-induced inhibition of Beclin1 would theoretically inhibit ER + breast carcinogenesis and promote tamoxifen sensitivity in ER + breast cancers.…”

Section: Mirnas and Drug Resistancementioning

confidence: 99%

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microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

Howard

Yang

2018

Biol Proced Online

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As de novo and acquired resistance to standard first line endocrine therapies is a growing clinical challenge for estrogen receptor-positive (ER+) breast cancer patients, understanding the mechanisms of resistance is critical to develop novel therapeutic strategies to prevent therapeutic resistance and improve patient outcomes. The widespread post-transcriptional regulatory role that microRNAs (miRNAs) can have on various oncogenic pathways has been well-documented. In particular, several miRNAs are reported to suppress ERα expression via direct binding with the 3’ UTR of ESR1 mRNA, which can confer resistance to estrogen/ERα-targeted therapies. In turn, estrogen/ERα activation can modulate miRNA expression, which may contribute to ER+ breast carcinogenesis. Given the reported oncogenic and tumor suppressor functions of miRNAs in ER+ breast cancer, the targeted regulation of specific miRNAs is emerging as a promising strategy to treat ER+ breast cancer and significantly improve patient responsiveness to endocrine therapies. In this review, we highlight the major miRNA-ER regulatory mechanisms in context with ER+ breast carcinogenesis, as well as the critical miRNAs that contribute to endocrine therapy resistance or sensitivity. Collectively, this comprehensive review of the current literature sheds light on the clinical applications and challenges associated with miRNA regulatory mechanisms and novel miRNA targets that may have translational value as potential therapeutics for the treatment of ER+ breast cancer.

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Section: Mirnas and Drug Resistancementioning

confidence: 99%

Section: Mirnas and Drug Resistancementioning

confidence: 99%

microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

Howard

Yang

2018

Biol Proced Online

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“…However, excessive autophagy activation in neurocytes damaged by I/R can lead to non-apoptotic cell death (19,20), which is called autoghagic programmed cell death. Beclin1 activates critical steps in autophagy, including the formation and maturation of autophagosomes (21,22). In addition, Bax and Bcl-2 have also been demonstrated to regulate autophagy (12).…”

Section: Introductionmentioning

confidence: 99%

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Liu

Zhu

et al. 2019

Exp Ther Med

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Dexmedetomidine (Dex) is a sedative and analgesic agent that is widely administered to patients admitted to the intensive care unit, and has been demonstrated to result in hypothermia. Many patients have been revealed to benefit from therapeutic hypothermia, which can mitigate cerebral ischemia/reperfusion (I/R) injury following successful cardiopulmonary resuscitation. However, studies investigating the efficacy of Dex in I/R treatment is lacking. The present study aimed to investigate the efficacy of Dex in mitigating neuronal damage, and to determine the possible mechanism of its effects in a rat model of cardiac arrest (CA). CA was induced in Sprague-Dawley rats by asphyxiation for 5 min. Following successful resuscitation, the surviving rats were randomly divided into two treatment groups; one group was intraperitoneally administered with Dex (D group), whereas the control group was treated with normal saline (N group). Critical parameters, including core temperature and blood pressure were monitored following return of spontaneous circulation (ROSC). Arterial blood samples were collected at 10 min after surgery (baseline) 30 and 120 min post-ROSC; and neurological deficit scores (NDS) of the rats were taken 12 or 24 h after ROSC prior to euthanasia. The hippocampal tissue was then removed for analysis by histology, electron microscopy and western blotting. Rats in the D group exhibited a lower core temperature and higher NDS scores compared with the N group (P<0.05). In addition, Dex injection resulted in reduced expression of apoptotic and autophagy-associated factors in the hippocampus (P<0.05). Dex treatment induced hypothermia and improved neurological function in rats after ROSC following resuscitation from CA by inhibiting neuronal apoptosis and reducing autophagy, which suggested that Dex may be a potential therapy option for patients with CA.

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“…For example, high expression of the GATA binding protein 3 gene has been reported to be associated with prolonged progression-free survival in patients with ER+ breast cancer (4). Furthermore, patients with a reduced level of Beclin 1 expression demonstrated a higher sensitivity to tamoxifen and a prolonged survival time (5). In addition, a high protein expression level of enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) has been reported to be associated with the development of distant metastases in breast cancer (6).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic signature predicts the distant relapse in patients with ER+ breast cancer treated with tamoxifen for five years

Zhou

Guo

2017

Mol Med Report

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Tamoxifen is the most commonly used drug to treat estrogen receptor positive (ER+) breast cancer. However, many patients with ER+ breast cancer have experienced resistance and other adverse side effects following treatment with tamoxifen. Furthermore, clinical and pathological parameters have thus far failed to predict the efficiency of tamoxifen administration. Therefore, gene signature based models for the prediction of survival time of such patients are urgently needed. In the current study, gene expression levels and follow‑up information of samples from GSE17705 and GSE22219 databases were used to construct a risk score model based on Cox multivariate regression. The expression levels of 10 genes were included in the model: CCNB2, CCNA2, FOXD1, WSB2, RBPMS, CTDSP1, BIN3, SLBP, EPRS, FTO. The samples in the high‑risk group had a relative early distant relapse time period (median survival time of 3.75 years) compared with the patients in the low risk group (median survival time of 6.5 years, P<0.01). For further validation, a further two independent datasets (GSE26971, GSE58644) were assessed. The overall survival time period of patients with high‑risk scores in these datasets was significantly longer than those with low‑risk scores (P<0.01). Furthermore, the associations between clinical parameters and risk score were investigated, and it was revealed that the risk score was significantly correlated with tumor age, tumor stage and grade. In addition, a 5‑year survival nomogram was plotted in order to facilitate the utilization of risk score along with other clinical data. In summary, using the transcriptomic profile, a multi‑gene expression based risk score was developed and was revealed as being able to successfully predict the outcome of patients with ER+ breast cancer treated with tamoxifen for 5 years.

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Lower Beclin 1 downregulates HER2 expression to enhance tamoxifen sensitivity and predicts a favorable outcome for ER positive breast cancer

Cited by 38 publications

References 70 publications

microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

microRNA Regulation in Estrogen Receptor-Positive Breast Cancer and Endocrine Therapy

Hypothermic properties of dexmedetomidine provide neuroprotection in rats following cerebral ischemia‑reperfusion injury

Transcriptomic signature predicts the distant relapse in patients with ER+ breast cancer treated with tamoxifen for five years

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