The role of EMT-related lncRNA in the process of triple-negative breast cancer metastasis

Zhang, Haomeng; Wang, Jiao; Yin, Yulong; Meng, Qi; Lyu, Yonggang

doi:10.1042/bsr20203121

Cited by 24 publications

(19 citation statements)

References 83 publications

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“…It is widely acknowledged that the epithelial-mesenchymal transition (EMT) is the most important step that leads to the metastasis of malignant tumors, including TNBC [ 11 ]. EMT is the process of polar epithelia transforming into the cells capable of free movement, which enhances the invasiveness of tumor cells into peripheral circulation [ 12 ]. It is recently found that EMT is closely related to multiple signaling pathways including Notch, Hedgehog, PI3K/AKT, and Wnt/ β -catenin pathways, revealing its key position in TNBC development and great potential in improving clinical outcome of TNBC patients [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

Guo

et al. 2021

Journal of Oncology

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Background. Triple-negative breast cancer (TNBC) remains the most incurable subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. It is generally acknowledged that epithelial-mesenchymal transition (EMT) is the key step in tumor metastasis. Methods. With the application of TCGA and GEO databases, we identified EMT-related lncRNAs by the Cox univariate regression analysis. Optimum risk scores were calculated and used to divide TNBC patients into high-/low-risk subgroups by the median value using the Lasso regression analysis. The Kaplan–Meier and ROC curve analyses were applied for model validation. Then, we assessed the risk model from multi-omic aspects including immune infiltration, drug sensitivity, mutability spectrum, signaling pathways, and clinical indicators. We also analyzed the expression pattern of lncRNAs involved in the model using qRT-PCR in TNBC cell lines and constructed the ceRNA network. Results. The risk model was composed of EMT-related long noncoding RNAs (lncRNAs), which seemed to be valuable in the prognostic prediction of TNBC patients. The model could act as an independent prognostic factor of TNBC and showed a robust prognostic ability in the stratification analysis. Further investigation demonstrated that the expression of lncRNAs was different between high aggressive and low aggressive TNBC cell lines, as well as TNBC patients. Conclusions. Together, our study successfully established a risk model with great accuracy and efficacy in the prognostic prediction of TNBC patients.

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Section: Introductionmentioning

confidence: 99%

Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

Guo

et al. 2021

Journal of Oncology

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“…At present, there are thousands of LncRNA genes involved in mammalian gene activities. The mechanism of LncRNA in regulating gene expression is mainly achieved via epigenetics, transcriptional regulation, and post-transcriptional regulation ( 13 , 14 ). In particular, the transcription regulation of LncRNA can interfere with the expression of its downstream genes and impact the activity of other transcription factors.…”

Section: Introductionmentioning

confidence: 99%

LncRNA ENST869 Targeting Nestin Transcriptional Region to Affect the Pharmacological Effects of Chidamide in Breast Cancer Cells

et al. 2022

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Breast cancer is one of the leading threats to the health of women. It has the highest incidence and mortality in women worldwide. Although progress has been made in the development and application of anti-breast cancer drugs such as Chidamide and others, the occurrence of drug resistance limits the effective application of chemotherapies. The purpose of this study is to explore the role of LncRNA in the pharmacological effect of Chidamide in breast cancer therapy. The human breast cancer MCF-7 or MDA-MB-231 cells were used as the research cell models. The RNA library screening and high-throughput sequencing comparative analysis was conducted. The binding of LncRNA and its downstream target genes in RNA and protein levels was tested. The results showed that the expression of LncRNA ENST869 in cells treated with Chidamide increased significantly, as demonstrated by real-time PCR and cell viability assay. RNAplex analysis showed that LncRNA ENST869 and Nestin mRNA may interact. RNA interference and Western blot analysis indicated that LncRNA ENST869 could target and regulate the expression of Nestin. Luciferase assay and RNA-protein pulldown showed that LncRNA ENST869 affected Nestin transcription. There might be a highly active binding region of LncRNA ENST869 in regulating Nestin transcriptional activity within the site of 250 bp upstream of the transcription starting point of Nestin. In addition, LncRNA ENST869 did not directly interact with Nestin protein to affect its activity. In conclusion, our results demonstrated that LncRNA ENST869 could affect the function of Nestin in breast cancer cells treated with Chidamide. Nestin is a key player in influencing the pharmacological activity of Chidamide and an essential factor in drug resistance of breast cancer cells.

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“…Clinically, breast cancers are classified according to specific subtypes defined by their histopathological features, and their expression of hormone receptors and growth factors, such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). ER-positive breast cancer is increasing in incidence, while the triple negative causes concern about its aggressiveness and ability to give rise to metastases [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Sci. 2021, 11, x FOR PEER REVIEW 2 of 12 triple negative causes concern about its aggressiveness and ability to give rise to metastases [4,5]. The use of cytotoxic chemotherapy in breast cancer has made significant progress in recent years due to the use of drugs able to interfere with the numerous biological pathways involved in cancer cell growth.…”

Section: Introductionmentioning

confidence: 99%

A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

et al. 2021

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Breast cancer is still considered a high-incidence disease, and numerous are the research efforts for the development of new useful and effective therapies. Among anticancer drugs, carbazole compounds are largely studied for their anticancer properties and their ability to interfere with specific targets, such as microtubule components. The latter are involved in vital cellular functions, and the perturbation of their dynamics leads to cell cycle arrest and subsequent apoptosis. In this context, we report the anticancer activity of a series of carbazole analogues 1–8. Among them, 2-nitrocarbazole 1 exhibited the best cytotoxic profile, showing good anticancer activity against two breast cancer cell lines, namely MCF-7 and MDA-MB-231, with IC50 values of 7 ± 1.0 and 11.6 ± 0.8 μM, respectively. Furthermore, compound 1 did not interfere with the growth of the normal cell line MCF-10A, contrarily to Ellipticine, a well-known carbazole derivative used as a reference molecule. Finally, in vitro immunofluorescence analysis and in silico studies allowed us to demonstrate the ability of compound 1 to interfere with tubulin organization, similarly to vinblastine: a feature that results in triggering MCF-7 cell death by apoptosis, as demonstrated using a TUNEL assay.

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The role of EMT-related lncRNA in the process of triple-negative breast cancer metastasis

Cited by 24 publications

References 83 publications

Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

Development of a Prognostic Model Based on the Identification of EMT-Related lncRNAs in Triple-Negative Breast Cancer

LncRNA ENST869 Targeting Nestin Transcriptional Region to Affect the Pharmacological Effects of Chidamide in Breast Cancer Cells

A Nitrocarbazole as a New Microtubule-Targeting Agent in Breast Cancer Treatment

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