Knockdown of circ_0006528 Suppresses Cell Proliferation, Migration, Invasion, and Adriamycin Chemoresistance via Regulating the miR-1236-3p/CHD4 Axis in Breast Cancer

Hao, Jie; Du, Xiaoping; Lv, Fengyan; Shi, Qinying

doi:10.1016/j.jss.2020.10.031

Cited by 32 publications

(19 citation statements)

References 30 publications

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“…In the recent study, Hao et al showed that miR-1236-3p hindered BC cell proliferation and metastasis, as well as adriamycin chemoresistance [29]. Consistent with previous reports [16,29], the anti-cancer effect of miR-1236-3p in BC was also confirmed in our study, which showed that cell proliferation, metastasis and glycolysis abilities were significantly repressed. Not only that, the rescue experiments suggested that the inhibitor of miR-1236-3p abolished the regulation of sh-circ_0102273 on BC progression, which further revealed that circ_0102273 sponged miR-1236-3p to mediate BC progression.…”

Section: Discussionsupporting

confidence: 93%

Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis

Luo

Liu

2022

Anti-Cancer Drugs

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The key regulatory roles of circular RNAs (circRNAs) in human diseases have been demonstrated, including breast cancer (BC). The purpose of this study is to explore the role of circ_0102273, a newly discovered circRNA, in BC progression. The expression levels of circ_0102273, microRNA (miR)-1236-3p and 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3) were determined by quantitative real-time PCR. Cell proliferation, migration and invasion were measured using colony formation assay, EdU staining, wound healing assay and transwell assay. Glucose consumption, lactate production and ATP level were detected to evaluate cell glycolysis. The interaction between miR-1236-3p and circ_0102273 or PFKFB3 was confirmed by dual-luciferase reporter assay and RIP assay. Additionally, western blot analysis was utilized for measuring PFKFB3 protein expression. In-vivo experiments were performed to further explore the function of circ_0102273 in BC tumorigenesis. Our data showed that circ_0102273 was highly expressed in BC tumor tissues and cells, and its downregulation could inhibit BC cell proliferation, metastasis and glycolysis. MiR-1236-3p was confirmed to be sponged by circ_0102273, and its inhibitor could reverse the negative regulation of sh-circ_0102273 on BC cell proliferation, metastasis and glycolysis. PFKFB3 could be targeted by miR-1236-3p, and its expression could be positively regulated by circ_0102273. In addition, miR-1236-3p could suppress BC cell proliferation, metastasis and glycolysis, while this effect could be abolished by PFKFB3. Furthermore, circ_0102273 knockdown also had been discovered to reduce BC tumorigenesis in vivo. In summary, our research proposed that circ_0102273 might be a potential target for BC treatment, which could inhibit BC proliferation, metastasis and glycolysis through the miR-1236-3p/PFKFB3 axis.

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Section: Discussionsupporting

confidence: 93%

Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis

Luo

Liu

2022

Anti-Cancer Drugs

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“…By next-generation sequencing and bioinformatics analysis, Gao et al [59,60] found that circ_0006528 expression was significantly up-regulated in ADM-resistant BC cells and tissues, and over-expression of circ_0006528 could contribute to ADM resistance via the miR-7-5p/Raf1 axis and indirect activation of MAPK/ERK signaling pathway. Another study also verified that circ_0006528 could contribute to ADM resistance to BC cells via modulating the miR-1236-3p/CHD4 axis [61]. Interestingly, circ_0006528 was also found to be involved in PTX resistance to BC cells by modulating miR-1299/CDK8 axis [62].…”

Section: The Dysregulation Of Circrnas Is Related To Drug Resistance ...mentioning

confidence: 73%

Circular RNAs: novel regulators of resistance to systemic treatments in breast cancer

Guo¹,

Hua²

2022

neo

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Systematic treatments including chemotherapy, endocrine therapy, and HER2-targeted therapy are important therapeutic approaches to breast cancer. However, drug resistance is a major barrier to achieving cure in breast cancer (BC) patients. Hence, it is urgent to gain insight into the drug-resistance mechanisms in order to improve the prognosis of BC patients. Genetic alternations, epigenetic alternations, and other non-genetic mechanisms such as BC stem-like cells, metabolic reprogramming, and tumor microenvironment contribute to drug resistance of BC. With the development of single-cell sequencing of circulating tumor cell and next-generation sequencing of matched pre-and post-progression tumor biopsies or ctDNA from BC patients with drug resistance, new mechanisms of resistance are being discovered. An increasing number of microRNAs and long non-coding RNAs have been found to be associated with the drug resistance of BC. However, there are few reports on the role of circular RNAs (circRNAs) as master regulators of drug resistance.Therefore, there is still much to say in the field of drug resistance-related circRNAs. In this review, we mainly focus on literature evidence for the detailed mechanisms associated with systematic expression of tumor suppressive circRNAs or knockdown of oncogenic circRNAs has been verified to reverse drug resistance of BC cells, which highlights that circRNAs may function as potential biomarkers and/or therapeutic targets of BC. Treatment targeting abnormally expressed circRNAs alone or combined with other systemic treatments may be a promising approach to conquering drug resistance.

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“…Recently, multiple studies have demonstrated that circRNAs play crucial roles in drug resistance in malignant tumors including breast cancer. For instance, it was reported that upregulated hsa_circ_0006528 contributed adriamycin-resistant in breast cancer via the miR-1236-3p/CHD4 axis and circABCB10 was overexpressed in breast cancer that was involved in paclitaxel resistance through the circRNA/let-7a-5p/DUSP7 axis [ 34 , 35 ]. Moreover, Sang et al demonstrated that hsa_circ_0025202 functioned as a tumor suppressor circRNA in HR-positive breast cancer, which increased sensitivity of breast cancer to tamoxifen treatment via regulating the miR-182-5p/FOXO3a axis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer

et al. 2022

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Background Approximate 25% HER2-positive (HER2+) breast cancer (BC) patients treated with trastuzumab recurred rapidly. However, the mechanisms underlying trastuzumab resistance remained largely unclear. Methods Trastuzumab-resistant associated circRNAs were identified by circRNAs high-throughput screen and qRT-PCR in HER2+ breast cancer tissues with different trastuzumab response. The biological roles of trastuzumab-resistant associated circRNAs were detected by cell vitality assay, colony formation assay, Edu assay, patient-derived xenograft (PDX) models and orthotopic animal models. For mechanisms research, the co-immunoprecipitation, Western blot, immunofluorescence, and pull down assays confirmed the relevant mechanisms of circRNA and binding proteins. Results We identified a circRNA circCDYL2, which was overexpressed in trastuzumab-resistant patients, which conferred trastuzumab resistance in breast cancer cells in vitro and in vivo. Mechanically, circCDYL2 stabilized GRB7 by preventing its ubiquitination degradation and enhanced its interaction with FAK, which thus sustained the activities of downstream AKT and ERK1/2. Trastuzumab-resistance of HER2+ BC cells with high circCDYL2 could be reversed by FAK or GRB7 inhibitor. Clinically, HER2+ BC patients with high levels of circCDYL2 developed rapid recurrence and had shorter disease-free survival (DFS) and overall survival (OS) following anti-HER2 therapy compared to those with low circCDYL2. Conclusions circCDYL2-GRB7-FAK complex plays a critical role in maintaining HER2 signaling, which contributes to trastuzumab resistance and circCDYL2 is a potential biomarker for trastuzumab-resistance in HER2+ BC patients.

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Knockdown of circ_0006528 Suppresses Cell Proliferation, Migration, Invasion, and Adriamycin Chemoresistance via Regulating the miR-1236-3p/CHD4 Axis in Breast Cancer

Cited by 32 publications

References 30 publications

Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis

Knockdown of circ_0102273 inhibits the proliferation, metastasis and glycolysis of breast cancer through miR-1236-3p/PFKFB3 axis

Circular RNAs: novel regulators of resistance to systemic treatments in breast cancer

circCDYL2 promotes trastuzumab resistance via sustaining HER2 downstream signaling in breast cancer

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