Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, progn...Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.展开更多
Cancer initiation and development engage extremely complicated pathological processes which involve alterations of a large number of cell signaling cascades and functional networks in temporal and spatial orders. Duri...Cancer initiation and development engage extremely complicated pathological processes which involve alterations of a large number of cell signaling cascades and functional networks in temporal and spatial orders. During last decades, microR NAs(miR NAs), a class of noncoding RNAs, have emerged as critical players in cancer pathogenesis and progression by modulating many pathological aspects related to tumor development, growth, metastasis, and drug resistance. The major function of miR NAs is to post-transcriptionally regulate gene expression depending on recognition of complementary sequence residing in target mR NAs. Commonly, a particular mi RNA recognition sequence could be found in a number of genes, which allows a single miR-NA to regulate multiple functionally connected genes simultaneously and/or chronologically. Furthermore, a single gene can be targeted and regulated by multiple miR NAs. However, previous studies have demonstrated that mi RNA functions are highly context-dependent,which leads to distinct pathological outcomes in different types of cancer as well as at different stages by alteration of the same miR NA. Here we summarize recent progress in studies on miR NA function in cancer initiation, metastasis and therapeutic response, focusing on breast cancer. The varying functions of mi RNAs and potential application of using miR NAs as biomarkers as well as therapeutic approaches are further discussed in the context of different cancers.展开更多
Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected ...Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.展开更多
Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like pheno...Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.展开更多
The surgical treatment of localized breast cancer has become progressively less aggressive over the years.The management of the axillary lymph nodes has been modified by the introduction of sentinel lymph node biopsy....The surgical treatment of localized breast cancer has become progressively less aggressive over the years.The management of the axillary lymph nodes has been modified by the introduction of sentinel lymph node biopsy. Axillary dissection can be avoided in patients with sentinel lymph node negative biopsies. Based on randomized trials data, it has been proposed that no lymph node dissection should be carried out even in certain patients with sentinel lymph node positive biopsies. This commentary discusses the basis of such recommendations and cautions against a general omission of lymph node dissection in breast cancer patients with positive sentinel lymph node biopsies. Instead, an individualized approach based on axillary tumor burden and biology of the cancer should be considered.展开更多
The control of the half-life of m RNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of m RN...The control of the half-life of m RNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of m RNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a m RNA will be available for translation for a longer time, resulting in high levels of protein gene products, which may lead to prolonged responses that subsequently result in over-production of cellular mediators that participate in cancer. The stability of these m RNA is regulated at the 3'UTR level by different mechanisms involving m RNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly interconnected to each other and lead to steady state levels of target m RNAs. Compelling evidence also suggests that both m RNA binding proteins and regulatory RNAswhich participate to m RNA half-life regulation may be useful prognostic markers in breast cancers, pointing to a potential therapeutic approach to treatment of patients with these tumors. In this review, we summarize the main mechanisms involved in the regulation of m RNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy.展开更多
文摘Breast cancer(BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs(miR NAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through m RNA targeting and, thus, are involved in many biological processes encompassing apoptosis,cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. Mi RNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miR NAs in BC that are detected with the use of highthroughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miR NAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and,at the same time, accumulating evidence has underscored the possible contribution of miR NAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via mi RNA delivery and mi RNA inhibition. The purpose of this review is to explore the ontological role of miR NAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.
文摘Cancer initiation and development engage extremely complicated pathological processes which involve alterations of a large number of cell signaling cascades and functional networks in temporal and spatial orders. During last decades, microR NAs(miR NAs), a class of noncoding RNAs, have emerged as critical players in cancer pathogenesis and progression by modulating many pathological aspects related to tumor development, growth, metastasis, and drug resistance. The major function of miR NAs is to post-transcriptionally regulate gene expression depending on recognition of complementary sequence residing in target mR NAs. Commonly, a particular mi RNA recognition sequence could be found in a number of genes, which allows a single miR-NA to regulate multiple functionally connected genes simultaneously and/or chronologically. Furthermore, a single gene can be targeted and regulated by multiple miR NAs. However, previous studies have demonstrated that mi RNA functions are highly context-dependent,which leads to distinct pathological outcomes in different types of cancer as well as at different stages by alteration of the same miR NA. Here we summarize recent progress in studies on miR NA function in cancer initiation, metastasis and therapeutic response, focusing on breast cancer. The varying functions of mi RNAs and potential application of using miR NAs as biomarkers as well as therapeutic approaches are further discussed in the context of different cancers.
基金supported by National Natural Science Foundation of China(Grant No.:81560269)
文摘Objective: To study the regulatory effects of miR-21 on breast cancer cell line proliferation and invasion as well as the downstream target genes. Methods: Breast cancer cell lines MCF-7 were cultured and transfected with miR-21 mimics and the corresponding negative control mimics(NC mimics), and then MTS kits were used to detect cell viability. Transwell experiment was used to detect cell invasion ability, and fluorescence quantitative PCR was used to detect the expression of proliferation and invasion-related genes in cells. Results: 24 h after transfection of miR-21 mimics and NC mimics, cell OD value and the number of invasive cells of miR-21 group were significantly higher than those of NC group, and m RNA contents of PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK in cells were significantly lower than those of NC group. Conclusion: miR-21 can promote the proliferation and invasion of breast cancer cell lines, and its downstream target genes include PDCD-4, Fas L, PTEN, Rho B, Maspin, TIMP3 and RECK.
基金Supported by The Ligue Nationale contre le Cancer,to Puisieux A
文摘Growing evidence suggests that breast cancer cell plasticity arises due to a partial reactivation of epithelialmesenchymal transition(EMT) programs in order to give cells pluripotency, leading to a stemness-like phenotype. A complete EMT would be a dead end program that would render cells unable to fully metastasize to distant organs. Evoking the EMT-mesenchymal-toepithelial transition(MET) cascade promotes successful colonization of distal target tissues. It is unlikely that direct reprogramming or trans-differentiation without passing through a pluripotent stage would be thepreferred mechanism during tumor progression. This review focuses on key EMT transcriptional regulators, EMT-transcription factors involved in EMT(TFs) and the mi RNA pathway, which are deregulated in breast cancer, and discusses their implications in cancer cell plasticity. Cross-regulation between EMT-TFs and mi RNAs, where mi RNAs act as co-repressors or co-activators, appears to be a pivotal mechanism for breast cancer cells to acquire a stem cell-like state, which is implicated both in breast metastases and tumor recurrence. As a master regulator of mi RNA biogenesis, the ribonuclease type Ⅲ endonuclease Dicer plays a central role in EMTTFs/mi RNAs regulating networks. All these EMT-MET key regulators represent valuable new prognostic and predictive markers for breast cancer as well as promising new targets for drug-resistant breast cancers.
文摘The surgical treatment of localized breast cancer has become progressively less aggressive over the years.The management of the axillary lymph nodes has been modified by the introduction of sentinel lymph node biopsy. Axillary dissection can be avoided in patients with sentinel lymph node negative biopsies. Based on randomized trials data, it has been proposed that no lymph node dissection should be carried out even in certain patients with sentinel lymph node positive biopsies. This commentary discusses the basis of such recommendations and cautions against a general omission of lymph node dissection in breast cancer patients with positive sentinel lymph node biopsies. Instead, an individualized approach based on axillary tumor burden and biology of the cancer should be considered.
基金Supported by A fellowship from"Fondazione Umberto Veronesi" to Griseri Pthe French National Institute of Cancer(INCA)+1 种基金the French Association for Cancer Research(ARC)the Fondation de France,the Conseil Général des Alpes Maritimes,Roche France and The"Association pour la Recherche sur les Tumeurs du Rein(ARTu R)"
文摘The control of the half-life of m RNA plays a central role in normal development and in disease progression. Several pathological conditions, such as breast cancer, correlate with deregulation of the half-life of m RNA encoding growth factors, oncogenes, cell cycle regulators and inflammatory cytokines that participate in cancer. Substantial stability means that a m RNA will be available for translation for a longer time, resulting in high levels of protein gene products, which may lead to prolonged responses that subsequently result in over-production of cellular mediators that participate in cancer. The stability of these m RNA is regulated at the 3'UTR level by different mechanisms involving m RNA binding proteins, micro-RNA, long non-coding RNA and alternative polyadenylation. All these events are tightly interconnected to each other and lead to steady state levels of target m RNAs. Compelling evidence also suggests that both m RNA binding proteins and regulatory RNAswhich participate to m RNA half-life regulation may be useful prognostic markers in breast cancers, pointing to a potential therapeutic approach to treatment of patients with these tumors. In this review, we summarize the main mechanisms involved in the regulation of m RNA decay and discuss the possibility of its implication in breast cancer aggressiveness and the efficacy of targeted therapy.
