A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p

Majzoub, Rania El; Fayyad‐Kazan, Mohammad; Dine, Assaad Nasr El; Makki, Rawan; Hamade, Eva; Grée, René; Hachem, Ali; Talhouk, Rabih; Fayyad‐Kazan, Hussein; Badran, Bassam

doi:10.1007/s13258-019-00866-y

Cited by 21 publications

(13 citation statements)

References 51 publications

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“…MicroRNAs (miRNAs) are classified as noncoding RNA sequences with more than 20 nucleotide sequences, which are involved in distinct cellular processes, such as proliferation, differentiation, and apoptosis 5,6 . miR‐125a‐5p, which belongs to the miR‐125 family, has been reported as an important miRNA in cancer progression including BC 7 . Our previous study has indicated miR‐125a‐5p acts as a tumor suppressor in BC via regulating the BC susceptibility gene 1‐associated protein 1 (BAP1) 8 .…”

Section: Introductionmentioning

confidence: 99%

lncRNA CERS6‐AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR‐125a‐5p to upregulate BAP1 expression

Yan

Feng

et al. 2020

Molecular Carcinogenesis

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Long noncoding RNAs (lncRNAs) can act as oncogene and tumor suppressor genes in many types of cancers including breast cancer (BC). Our previous study has indicated microRNA (miR)‐125a‐5p was downregulated and function as a tumor suppressor in BC. However, its upstream regulation mechanism is still unclear. In this study, we used bioinformatics algorithms, RNA pulldown assay, and dual‐luciferase reports assay to predict and confirm lncRNA CERS6‐AS1 interacted with miR‐125a‐5p. Then we found CERS6‐AS1 was upregulated in BC tissues. Experimental results of tumor growth in nude mice show that CERS6‐AS1 promotes tumor growth. Furthermore, CERS6‐AS1 regulated BC susceptibility gene 1‐associated protein 1 (BAP1) expression via sponging miR‐125a‐5p via Western blot analysis and quantitative polymerase chain reaction arrays. Finally, we showed that miR‐125a‐5p had opposing effects to those of CERS6‐AS1 on BC cells, demonstrating that CERS6‐AS1 may promote cell proliferation and inhibit cell apoptosis via sponging miR‐125a‐5p. Our results indicated CERS6‐AS1 promote BC cell proliferation and inhibit cell apoptosis via sponging miR‐125a‐5p to upregulate BAP1 expression.

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Section: Introductionmentioning

confidence: 99%

lncRNA CERS6‐AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR‐125a‐5p to upregulate BAP1 expression

Yan

Feng

et al. 2020

Molecular Carcinogenesis

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“…For individuals, each miRNA also regulates the progression of TNBC in previous experimental studies by up- or downregulation of expression levels. Among them, 5 miRNAs upregulated in TNBC improve the metastasis progression of TNBC (such as miR-107, miR-20a-5p, and miR-455-3p) 36 - 38 , proliferation (such as miR146b-5p and miR-455-3p) 32 , 38 , and apoptosis (such as miR-20a-5p and miR-324-5p) 39 , 40 . The downregulated miRNAs were miR-139-5p, miR-10b-5p, and miR486-5p, which are involved in chemoresistance and metastasis 31 , 41 - 46 .…”

Section: Discussionmentioning

confidence: 99%

A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse

et al. 2020

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Rationale: Triple-negative breast cancer (TNBC), which has the highest recurrence rate and shortest survival time of all breast cancers, is in urgent need of a risk assessment method to determine an accurate treatment course. Recently, miRNA expression patterns have been identified as potential biomarkers for diagnosis, prognosis, and personalized therapy. Here, we investigate a combination of candidate miRNAs as a clinically applicable signature that can precisely predict relapse in TNBC patients after surgery. Methods: Four total cohorts of training (TCGA_TNBC and GEOD-40525) and validation (GSE40049 and GSE19783) datasets were analyzed with logistic regression and Gaussian mixture analyses. We established a miRNA signature risk model and identified an 8-miRNA signature for the prediction of TNBC relapse. Results: The miRNA signature risk model identified ten candidate miRNAs in the training set. By combining 8 of the 10 miRNAs (miR-139-5p, miR-10b-5p, miR-486-5p, miR-455-3p, miR-107, miR-146b-5p, miR-324-5p and miR-20a-5p), an accurate predictive model of relapse in TNBC patients was established and was highly correlated with prognosis (AUC of 0.80). Subsequently, this 8-miRNA signature prognosticated relapse in the two validation sets with AUCs of 0.89 and 0.90. Conclusion: The 8-miRNA signature predictive model may help clinicians provide a prognosis for TNBC patients with a high risk of recurrence after surgery and provide further personalized treatment to decrease the chance of relapse.

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“…TNBC lacks the expression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) (2). TNBC comprises 10-20% of breast cancer cases and is responsible for 25% of breast cancer-related deaths (3). Numerous studies exploring potentially effective medicines and therapeutic strategies for TNBC have been performed (2)(3)(4); however, conventional chemotherapy is still the most common method for treating TNBC patients (5).…”

Section: Introductionmentioning

confidence: 99%

Curcumol enhances the anti-tumor effects of metformin via suppressing epithelial-mesenchymal transition in triple-negative breast cancer

Wang¹,

Dong²,

Liu³

2020

Ann Transl Med

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Background: Triple-negative breast cancer (TNBC) is a severe disease with a high mortality rate.Metformin has been found to possess anti-tumor properties. Curcumol, an active ingredient extracted from curcuma, exerts the protective effect in TNBC cells through inducing apoptosis. However, the effects of curcumol combined with metformin on the treatment of TNBC have yet to be fully established.Methods: TNBC cells MDA-MB-231 and MDA-MB-468 cells were used in the study. TNBC cells were treated with curcumol and metformin alone or treated with curcumol combined with metformin.Cell viability was determined using Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The levels of proteins were measured using Western blot. Wound healing assay and Transwell invasion assays were used to determine cell migration and invasion ability, respectively. A xenograft model was established to investigate the tumor growth ability. Immunohistochemistry was performed to determine the expression of Ki-67 and Vascular endothelial growth factor (VEGF).Results: In the study, the administration of curcumol alone had no significant effects on the TNBC cells.However, the anti-proliferation, anti-metastasis, and anti-epithelial-mesenchymal transition (EMT) effects of metformin were enhanced by the addition of curcumol. Further, curcumol reversed TNBC cell proliferation, migration, invasion, and EMT induced by rucaparib, and enhanced the effect of metformin on rucaparibinduced TNBC cells. The combination of curcumol and metformin also suppressed tumor growth, EMT marker expression, and the activation of Wnt2/β-Catenin signaling during in vivo experiments. Conclusions:The combination of curcumol and metformin enhances the anti-tumor effects of metformin on TNBC via inhibiting EMT. Curcumol combined with metformin may hold promise as a therapeutic strategy for TNBC.

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A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p

Cited by 21 publications

References 51 publications

lncRNA CERS6‐AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR‐125a‐5p to upregulate BAP1 expression

lncRNA CERS6‐AS1 as ceRNA promote cell proliferation of breast cancer by sponging miR‐125a‐5p to upregulate BAP1 expression

A panel of eight microRNAs is a good predictive parameter for triple-negative breast cancer relapse

Curcumol enhances the anti-tumor effects of metformin via suppressing epithelial-mesenchymal transition in triple-negative breast cancer

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