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1.
World J Surg Oncol ; 22(1): 243, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256855

RESUMO

OBJECTIVE: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. PATIENTS AND METHODS: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. RESULTS: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470-21.569), PR (OR = 7.690, 95%CI: 3.974-16.129, Her-2 (OR = 10.489, 95%CI: 2.779-23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031-0.377 were significant independent risk factors affecting AR expression. CONCLUSIONS: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Recidiva Local de Neoplasia , Receptor ErbB-2 , Receptores Androgênicos , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Receptores Androgênicos/metabolismo , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Prognóstico , Adulto , Receptores de Progesterona/metabolismo , Receptor ErbB-2/metabolismo , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Receptores de Estrogênio/metabolismo , Seguimentos , Idoso , Estudos Retrospectivos , Metástase Linfática , Estadiamento de Neoplasias , Gradação de Tumores , Idoso de 80 Anos ou mais
2.
Cancer Cell Int ; 24(1): 284, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39135158

RESUMO

BACKGROUND: Obesity and the forkhead box O1(FOXO1) affect the survival of breast cancer patients, but the underlying mechanism remains unclear. We aimed to investigate the role of FOXO1 in obesity-associated-breast cancer. METHODS: We screened 383 breast disease patients from the first affiliated hospital with Nanjing Medical University in 2020. We performed wound healing, transwell, matrigel assays to assess the metastatic ability of cancer cells. We adopted mRNAs sequencing to select the differentially expressed transcripts in breast cancer. We applied immunohistochemistry, western blot, tissue microarrays to assess the level of FOXO1 and epithelial-mesenchymal transition (EMT) pathways. We conducted bioinformatic analysis to investigate interactions between FOXO1 and miR-135b. We used fluorescence in situ hybridization, RT-qPCR to confirm the characteristics of circCNIH4. We conducted luciferase reporter assay, rescue experiments to investigate interactions between circCNIH4 and miR-135b. RESULTS: Obesity was positively correlated with the incidence and progression of breast cancer. Adipocytes enhanced the migration of breast cancer and attenuated the effects of FOXO1. MiR-135b was a binding gene of FOXO1 and was regulated by circCNIH4. CircCNIH4 exhibited antitumor activity in vitro and in vivo. CONCLUSION: Adipocytes might accelerate the progression of breast cancer by modulating FOXO1/miR-135b/ circCNIH4 /EMT axis and regulating copper homeostasis.

3.
Aging (Albany NY) ; 16(14): 11434-11445, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39068670

RESUMO

BACKGROUND: The expression patterns and prognostic value of Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) family genes in breast cancer remain to be elucidated. METHODS: The expression levels, prognostic value, and biological function of PLODs were determined using Oncomine, cBioPortal, GEPIA, Timer, UALCAN, PrognoScan, GeneMANIA, Metascape, and breast cancer tissue microarrays. RESULTS: The expressions of PLOD1 and PLOD3 were upregulated in breast cancer tissues, indicating worse clinical stages. High expression levels of PLOD family genes were associated with worse disease-free survival and distant metastasis-free survival, while high expression levels of PLOD1 and PLOD3 were related to worse overall survival in all breast cancer patients. The levels of PLOD family genes were all significantly higher in the age ≤51 y group, HR-negative patients, and triple negative breast cancer (TNBC) patients. They are associated with tumor-infiltrating immune cells (TIICs), including CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells. According to co-expression gene analysis and functional enrichment, they are associated with protein hydroxylation, collagen biosynthesis and modifying enzymes, collagen metabolism, RNA splicing, extracellular matrix organization, VEGFA-VEGFR2 signaling pathway, and skeletal system development. Immunohistochemistry showed that the expressions of all PLOD family genes were significantly elevated in breast cancer tissues. PLOD1 expression was positively correlated with ER, TNBC status, and tumor grade. PLOD2 expression was positively connected with Ki-67 status. PLOD3 expression was positively related with age and tumor grade. CONCLUSIONS: PLOD family genes are novel potential prognostic biomarkers for breast cancer, and targeting PLOD inhibitors might be an effective strategy for breast cancer therapy.


Assuntos
Neoplasias da Mama , Regulação Neoplásica da Expressão Gênica , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase , Humanos , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/genética , Pró-Colágeno-Lisina 2-Oxoglutarato 5-Dioxigenase/metabolismo , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Prognóstico , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo
4.
Int Immunopharmacol ; 133: 112093, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38669947

RESUMO

BACKGROUND: IFI30 is a lysosomal thiol reductase involved in antigen presentation and immune regulation in various cancers, including breast cancer. Despite its known involvement, the precise mechanism, function, and relationship with the PD-L1 axis and immune response remain unclear. METHODS: We conducted an extensive investigation into IFI30 mRNA expression in breast cancer utilizing data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. Furthermore, we characterized IFI30 mRNA expression across various cell types using publicly available single-cell RNA sequencing datasets, and assessed protein expression through immunohistochemistry using an in-house breast cancer tissue microarray. Functional experiments were performed to elucidate the effects of IFI30 overexpression on PD-L1 expression and inhibitory efficacy in both macrophages and breast tumor cells. RESULTS: Our study unveiled a marked upregulation of IFI30 expression in breast cancer tissues compared to their normal counterparts, with notable associations identified with tumor stage and prognosis. Additionally, IFI30 expression demonstrated significant correlations with various immune-related signaling pathways, encompassing peptide antigen binding, cytokine binding, and MHC class II presentation. Notably, breast cancer samples exhibiting high IFI30 expression in tumor cells displayed high PD-L1 expression on corresponding cells, alongside a diminished ratio of CD8 + T cell infiltration within the tumor microenvironment. Furthermore, ectopic knockdown of IFI30 in both tumor cells and macrophages resulted in a reduction of PD-L1 expression, while conversely, overexpression of IFI30 led to an increase in PD-L1 expression. CONCLUSIONS: This study offers new insights into the involvement of IFI30 in breast cancer, elucidating its interplay with the PD-L1 axis and immune response dynamics. Our findings suggest that modulation of the IFI30-PD-L1 axis could serve as a promising strategy for regulating T cells infiltration in breast cancer thus treating breast cancer.


Assuntos
Antígeno B7-H1 , Neoplasias da Mama , Imunoterapia , Oxirredutases atuantes sobre Doadores de Grupo Enxofre , Feminino , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Neoplasias da Mama/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Macrófagos/imunologia , Macrófagos/metabolismo , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/genética , Oxirredutases atuantes sobre Doadores de Grupo Enxofre/metabolismo , Prognóstico
5.
Eur J Pharmacol ; 963: 176221, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38128869

RESUMO

We identified circNFIB (hsa_circ_0086376) as a down-regulated circRNA in breast cancer but its effect is unclear. We aimed to explore the roles of circNFIB in breast cancer. The expression levels of circNFIB in breast cancer tissues and cells were detected. Both in vitro and in vivo experiments were used to assess the effects and mechanisms of circNFIB. circNFIB was down-regulated in 29 breast cancer tissues compared to adjacent normal tissues. circNFIB is a highly conserved circRNA and mainly located in cytoplasm of breast cancer cells. In vitro experiments showed that overexpression of circNFIB inhibited proliferation and invasion of breast cancer cells, whereas knockdown of circNFIB induced proliferation and invasion. Animal experiments indicated that circNFIB inhibited tumor growth and metastasis in vivo. Bioinformatics analysis showed that circNFIB contained an open reading frame (ORF) spanning its spliced junction, an internal ribosome entry site (IRES) and a N6-methyladenosine (m6A) site, suggesting circNFIB had the potential to encode a 56 amino acid (aa) protein, which was then confirmed by experiments. Metabonomics analysis results indicated that circNFIB may inhibit synthesis of arachidonic acid (AA) by regulating phospholipase. EIF4A3 and U2AF65 may regulate circNFIB expression by binding to the flanking sequence of circNFIB. In conclusion, circNFIB is a down-regulated circRNA in breast cancer tissues and encodes a 56 aa protein. circNFIB down-regulates AA in breast cancer cells, thus decreasing AA metabolites. Based on reported evidences of AA metabolites on cancer, we speculated that circNFIB may inhibit breast tumor growth and metastasis partly by inhibiting AA.


Assuntos
MicroRNAs , Animais , MicroRNAs/genética , RNA Circular/genética , Ácido Araquidônico , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
6.
Cancer Med ; 12(4): 5137-5149, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36426411

RESUMO

BACKGROUND: Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non-coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism-related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer. METHODS: 1222 RNA-seq were extracted from the TCGA database, and 74 glucose metabolism-related genes were loaded from the GSEA website. Then, 7 glucose metabolism-related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high-risk patients predict a poor clinical outcome with high reliability (P=2.838×10-6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle-related pathways were significantly enriched in a high-risk group. RESULTS: Our results showed that glucose metabolism-related lncRNAs can affect breast cancer progression. 7 glucose metabolism-related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high-risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. CONCLUSION: 7 glucose metabolism-related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple-negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets.


Assuntos
RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , RNA Longo não Codificante/genética , Amigos , Reprodutibilidade dos Testes , Glucose
7.
Medicine (Baltimore) ; 101(42): e31336, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281130

RESUMO

OBJECTIVE: The structural maintenance of chromosome (SMC) gene family, including 6 proteins, is involved in a wide range of biological functions in different human cancers. Nevertheless, there is little research on the expression patterns, potential functions and prognostic value of SMC genes in hepatocellular carcinoma (HCC). Based on publicly available databases and integrative bioinformatics analysis, we tried to determine the value of SMC gene expression in predicting the risk of developing HCC. METHODS: The expression and copy number variations data of SMC family members were obtained from TCGA (The Cancer Genome Atlas). We identified the prognostic values of SMC family members and their clinical features. GSEA (Gene Set Enrichment Analysis) was conducted to detect the mechanism underlying the involvement of SMC family members in liver cancer. We used Tumor Immune Estimation Resource database to explore the associations between TIICs (Tumor Immune Infiltrating Cells) and the SMC family members. RESULTS: Our analysis proved that downregulation of SMC family members was common modification in HCC patients. In HCC, the expression of SMC1A, SMC2, SMC3, SMC4, SMC6 were upregulated. Upregulation of SMC2, SMC3, and SMC4, along with the clinical stage of HCC, were associated with a poor prognosis according to the results of univariate and multivariate Cox proportional hazards regression analysis. SMC2, SMC3, and SMC4 are also related to tumor purity and immune infiltration levels of HCC. The GSEA results proved that SMC family members take part in numerous biological processes underlying tumorigenesis. CONCLUSION: In this study, we comprehensively analyzed the expression of SMC family members in patients with HCC. This can provide insights for further investigation of the SMC members as potential therapeutic targets in HCC and suggest that the use of SMC inhibitor targeting SMC2, SMC3, and SMC4 can be a practical strategy for the therapy of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Prognóstico , Neoplasias Hepáticas/patologia , Variações do Número de Cópias de DNA , Cromossomos/metabolismo
8.
Cancer Cell Int ; 22(1): 190, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578228

RESUMO

Extracellular vesicles secreted by tumor microenvironment (TME) cells are vital players in tumor progression through transferring nucleic acids and proteins. Macrophages are the main immune cells in TME and tumor associated macrophages (TAM) express M2 phenotype, which induce tumor proliferation, angiogenesis, invasion, metastasis and immune elimination, resulting in the subsequent evolution of malignancies. There are a high number of studies confirmed that tumor cells and TAM interact with each other through extracellular vesicles in various cancers, like pancreatic ductal adenocarcinoma, gastric cancer, breast cancer, ovarian cancer, colon cancer, glioblastoma, hepatocellular cancer, and lung cancer. Herein, this review summarizes the current knowledge on mechanisms of communications between tumor cells and TAM via extracellular vesicles, mainly about microRNAs, and targeting these events might represent a novel approach in the clinical implications of this knowledge into successful anti-cancer strategies.

9.
Nat Commun ; 13(1): 1091, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35232990

RESUMO

Kagome metal TbMn6Sn6 was recently discovered to be a ferrimagnetic topological Dirac material by scanning tunneling microscopy/spectroscopy measurements. Here, we report the observation of large anomalous Nernst effect and anomalous thermal Hall effect in this compound. The anomalous transverse transport is consistent with the Berry curvature contribution from the massive Dirac gaps in the 3D momentum space as demonstrated by our first-principles calculations. Furthermore, the transverse thermoelectric transport exhibits asymmetry with respect to the applied magnetic field, i.e., an exchange-bias behavior. Together, these features place TbMn6Sn6 as a promising system for the outstanding thermoelectric performance based on anomalous Nernst effect.

10.
Am J Transl Res ; 14(12): 8788-8792, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36628238

RESUMO

BACKGROUND: Malignant adenomyoepithelioma (MAME) of the breast is an extremely rare breast malignancy, in which they arise from either luminal epithelial or myoepithelial components, or both. At present, there is very little clinical data of MAME. CASE REPORT: We present two cases, one of them is a 34-year-old woman who underwent needle biopsy for a 3.2 cm-size mass in the right breast, and the pathology was MAME of breast. Another case is a 45-year-old woman who had a 3.0 cm-size mass in the right breast. We performed a breast-conserving surgery and sentinel lymph node biopsy, both of which were negative. The histopathology of these two cases was invasive carcinoma; however, these cases were eligible for MAME of the breast through combining with immunohistochemistry. CONCLUSIONS: MAME of the breast is very rare, and has a diverse cell morphology, which must be combined with immunohistochemistry to make a clear diagnosis. Besides, it should be differentiated from adenoid cystic cancer, malignant leafy tumor, spindle cell carcinoma, etc. The clinical characteristics and treatment strategies were further discussed in combination with the literature.

11.
Phys Rev Lett ; 127(24): 247202, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34951793

RESUMO

Two-dimensional (2D) van der Waals (vdW) magnets have been a fertile playground for the discovery and exploration of physical phenomena and new physics. In this Letter, we report the observation of an anomalous thermal Hall effect (THE) with κ_{xy}∼1×10^{-2} W K^{-1} m^{-1} in an insulating van der Waals ferromagnet VI_{3}. The thermal Hall signal persists in the absence of an external magnetic field and flips sign upon the switching of the magnetization. In combination with theoretical calculations, we show that VI_{3} exhibits a dual nature of the THE, i.e., dominated by topological magnons hosted by the ferromagnetic honeycomb lattice at higher temperatures and by phonons induced by the magnon-phonon coupling at lower temperatures. Our results not only position VI_{3} as the first ferromagnetic system to investigate both anomalous magnon and phonon THEs, but also render it as a potential platform for spintronics-magnonics applications.

12.
Cell Death Dis ; 12(5): 420, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33911067

RESUMO

Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a "miRNAs sponge" to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes ß-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan-Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-ß-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.


Assuntos
Ciclina D1/metabolismo , MicroRNAs/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , beta Catenina/metabolismo , Carcinogênese , Movimento Celular/fisiologia , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Humanos , MicroRNAs/genética , Metástase Neoplásica , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Circular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Microambiente Tumoral
13.
Transl Cancer Res ; 10(10): 4355-4364, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35116294

RESUMO

BACKGROUND: Stromal cells and immune cells in tumor microenvironment (TME) have been reported to have significant value in the diagnosis and prognosis of cancers. We aimed to identify key biomarkers predicting survival in the TME of breast cancer. METHODS: Cell type enrichment analysis was performed to estimate cell scores using the xCell method with gene expression data from public database. Least absolute shrinkage and selection operator (LASSO) regression was used to identify key signature from the cell scores. RESULTS: Totally, 50 cells in TME had different scores between 1,078 breast cancer tissues and 112 adjacent normal tissues. We identified a 4-cell signature predicting breast cancer survival, including myocytes, natural killer T cell (NKT), conventional dendritic cell (cDC) and sebocytes, which was validated in the test set. Further analysis showed that cDC score was a key signature predicting prognosis of breast cancer. cDC score was significantly associated with molecular classification and stage of breast cancer, as well as expression level of Ki67. Spearman's correlation analysis found that cDC score was inversely correlated with the expression level of HER2. High cDC score may predicate better pathological complete response rate. Mechanism analysis indicated high cDC score was associated with elevated immune activity; IL-2 was a key gene associated with high cDC score; and Breast cancer patients with high IL-2 expression had a longer survival time. CONCLUSIONS: In conclusion, cDC score was a key signature predicting prognosis for breast cancer. cDCs may exert antitumor effects by upregulating IL-2.

14.
Clin Genet ; 99(1): 84-92, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32583420

RESUMO

Long non-coding RNAs (lncRNAs), a class of long RNAs, are longer than 200 nucleotides in length but lack protein-coding capacity. LncRNAs, as critical genomic regulators, are involved in genomic imprinting regulation, histone modification and gene expression regulation as well as tumor initiation and progression. However, it is also found that lncRNAs are associated with drug resistance in several types of cancer. Drug resistance is an important reason for clinical chemotherapy failure, and the molecular mechanism of tumor resistance is complex, which is a process of multi-cause, multi-gene and multi-signal transduction pathway interaction. Then comprehending the mechanisms of chemoresistance will help find ways to control the tumor progression effectively. Therefore, in this review, we will construct lncRNAs /drug resistance interaction network and shed light on the role of lncRNAs in drug resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/tratamento farmacológico , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , MicroRNAs/genética , Neoplasias/genética , Neoplasias/patologia , Transdução de Sinais/genética
15.
Epigenomics ; 12(2): 101-125, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31920098

RESUMO

Aim: Circular RNAs (circRNAs) still have many potential functions in the process of tumor development that are not completely understood. The study aims to explore novel circRNAs and their mechanisms of action in breast cancer (BCa). Materials & methods: A combination strategy of RNA-sequencing (RNA-seq) technique, quantitative real-time PCR and bioinformatic analysis was employed to identify the potential mechanisms involving differentially expressed circRNAs in the serum exosomes and tissues of BCa patients. Results: The expression levels of hsa-circRNA-0005795 and hsa-circRNA-0088088 were significantly different both in serum exosomes and tissues and might function as competing endogenous RNAs and play vital roles in BCa development. Conclusion: We constructed two circRNA-miRNA networks and provided new insight into the prognosis and therapy of BCa using circRNAs from serum exosomes.


Assuntos
Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Exossomos/genética , Feminino , Ontologia Genética , Humanos , Prognóstico , RNA-Seq
16.
Epigenomics ; 12(4): 303-317, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31920104

RESUMO

Aim: We aimed to explore the roles of circular RNA, circVAPA in regulating cell migration and invasion of breast cancer. Materials & methods: CircVAPA expression was detected in breast cancer tissues and cells. The role of circVAPA was evaluated by MTT assay, wound-healing and transwell assay. The relationship between circVAPA and miR-130a-5p and the location of circVAPA were explored. Results: We discovered that circVAPA was dysregulated in breast cancer tissues and cells. Ectopic circVAPA regulated breast cancer migration, invasion and proliferation. CircVAPA was mainly expressed in the cytoplasm and could act as a miRNA sponge for miR-130a-5p, but did not regulate its parental gene. Conclusion: CircVAPA may promote migration and invasion capacity of breast cancer via harboring miR-130a-5p.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Invasividade Neoplásica/genética , RNA Circular/genética , RNA Circular/fisiologia
17.
J Cell Physiol ; 235(7-8): 5722-5735, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31970775

RESUMO

We aimed to investigate the role of exosomal miR-4443 in metastasis of breast cancer (BCa). In vitro wound-healing assay and transwell invasion assay were used to investigate effect of miR-4443 on BCa cells. Animal experiments were performed to confirm its effects in vivo. miR-4443 promotes the metastasis of BCa cells through downregulating tissue inhibitors of metalloproteinase 2 (TIMP2) and upregulating matrix metalloproteinases (MMPs). Highly invasive BCa cells have a higher expression of miR-4443 in both cells and exosomes. The exosomes derived from highly invasive BCa cells mainly gather in the primary tumor and liver. In vivo, overexpression of miR-4443 in noninvasive BCa cells induces liver metastasis, accompanied with downregulated TIMP2, and upregulated MMP-2 in both the primary tumor and liver. When we armed MCF-10A exosomes with miR-4443 inhibitors to treat mice bearing high-miR-4443 tumors, exosomes accumulated in the primary tumor, and liver following the upregulation of TIMP2 and downregulation of MMP2, and the metastasis was inhibited. Highly invasive BCa cells destroy natural barriers against metastasis by delivering exosomal miR-4443 to stromal cells of the primary tumor and impairing TIMP2, consequently activating MMP; circulating exosomal miR-4443 might promote BCa cells lodging in future metastatic sites through the similar mechanisms.


Assuntos
Neoplasias da Mama/genética , Neoplasias Hepáticas/genética , Metaloproteinase 2 da Matriz/genética , MicroRNAs/genética , Inibidor Tecidual de Metaloproteinase-2/genética , Animais , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Células MCF-7 , Camundongos , Metástase Neoplásica , Transdução de Sinais/genética , Microambiente Tumoral/genética
18.
Biosci Rep ; 39(6)2019 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-31160488

RESUMO

Breast cancer (BCa) is one of the most frequently diagnosed cancers and leading cause of cancer deaths among females worldwide. Circular RNAs (circRNAs) are a new class of endogenous regulatory RNAs characterized by circular shape resulting from covalently closed continuous loops that are capable of regulating gene expression at transcription or post-transcription levels. With the unique structures, circRNAs are resistant to exonuclease RNase R and maintain stability more easily than linear RNAs. Recently, an increasing number of circRNAs are discovered and reported to show different expression in BCa and these dysregulated circRNAs were correlated with patients' clinical characteristics and grade in the progression of BCa. CircRNAs participate in the bioprocesses of carcinogenesis of BCa, including cell proliferation, apoptosis, cell cycle, tumorigenesis, vascularization, cell invasion, migration as well as metastasis. Here we concentrated on biogenesis and function of circRNAs, summarized their implications in BCa and discussed their potential as diagnostic and therapeutic targets for BCa.


Assuntos
Apoptose , Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Ciclo Celular , Neovascularização Patológica/metabolismo , RNA Circular/metabolismo , RNA Neoplásico/metabolismo , Neoplasias da Mama/patologia , Carcinogênese/patologia , Feminino , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Proteínas de Neoplasias/metabolismo , Neovascularização Patológica/patologia , Estabilidade de RNA , Ribonuclease P/metabolismo
19.
Epigenomics ; 11(2): 199-213, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30657346

RESUMO

AIM: The study aimed to investigate the role of circular RNA circASS1 in breast cancer cells. MATERIALS & METHODS: Circular RNAs microarray expression profile were analyzed in MCF-7, MDA-MB-231, and qRT-PCR and western blotting were used to quantify expression of circASS1 and its parental gene ASS1. Wound healing, migration and invasion assay were performed. Luciferase assay system was used to detect harbored miRNA. RESULTS: CircASS1 in MDA-MB-231 is downregulated comparing to MCF-7, and overexpression of circASS1 could suppress invasion and migration. While silence, it could promote invasion and migration. MiR-4443 functioning as a tumor promoter gene could be captured by circASS1. ASS1 is upregulated in loss-of-function experiments, while downregulated in gain-of-function experiments. CONCLUSION: CircASS1 suppresses invasion and migration capacity of breast cancer cells and harbored miR-4443.


Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , RNA Circular/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Feminino , Humanos , Células MCF-7 , MicroRNAs/metabolismo , RNA Circular/metabolismo
20.
Epigenomics ; 10(11): 1499-1509, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309258

RESUMO

Exosomes are small membrane vesicles with a diameter of 40-100 nm, which are released into the intracellular environment. Exosomes could influence the genetic and epigenetic changes of receptor cells by promoting the horizontal transfer of various proteins or RNAs, especially miRNAs. Moreover, exosomes also play an important role in tumor microenvironment. Exosomes could promote the short- and long-distance exchanges of genetic information by acting as mediators of cell-to-cell communication. In addition, exosomes participate in drug resistance of tumor cells by genetic exchange between cells. It is reported that exosomes could be absorbed by recipient cells and transmit chemoresistance from drug-resistant tumor cells to sensitive ones. Then understanding the mechanisms of chemotherapy failure and controlling tumor progression effectively will be a major challenge for us. Therefore, in this review, we will briefly reveal the role of exosomes in drug resistance.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Exossomos/metabolismo , Neoplasias/metabolismo , Animais , Exossomos/genética , Humanos , MicroRNAs/genética , Neoplasias/genética
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