Dataset Information

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance and Applications in Human Triple-Negative Breast Cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3'-untranslated region (3'-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial-mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC.

SUBMITTER: Ding L

PROVIDER: S-EPMC6953059 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance and Applications in Human Triple-Negative Breast Cancer.

Ding Lei L Gu Huan H Xiong Xianhui X Ao Hongshun H Cao Jiaqi J Lin Wen W Yu Min M Lin Jie J Cui Qinghua Q

Cells 20191122 12

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3'-untranslated region (3'-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regula ...[more]

PMID: 31766744

Similar Datasets

Project description:BackgroundTriple-negative breast cancer (TNBC) is more commonly associated with young patients, featuring high histological grade, visceral metastasis, and distant recurrence. Follistatin (FST) is a secreted extracellular regulatory protein that antagonizes TGF-β superfamily such as activin and TGF-β related superfamily such as bone morphogenetic protein (BMP). The implication of FST in the proliferation, angiogenesis, and metastasis of solid tumors documents good or poor outcome of patients with BC. However, the role of FST in TNBC remains unclear.MethodsData of 935 patients with breast cancer (BC) were extracted from TCGA. Case-control study, Kaplan-Meier, uni-multivariate COX, and ROC curve were utilized to investigate the relationship between FST expression and the clinical characteristics and prognosis of BC. Functional studies were used to analyze the effect of FST expression on proliferation, apoptosis, migration, and invasion of TNBC cell lines. Bioinformatic methods such as volcanoplot, GO annd KEGG enrichment, and protein-protein interactions (PPI) analyses were conducted to further confirm the different roles of FST in the apoptotic pathways among mesenchymal and mesenchymal stem-like cells of TNBC.ResultsData from TCGA showed that low FST expression correlated with poor prognosis (for univariate analysis, HR = 0.47, 95% CI: 0.27-0.82, p = 0.008; for multivariate analysis, HR = 0.40, 95% CI: 0.21-0.75, p = 0.004). Low FST expression provided high predicted value of poor prognosis in TNBC amongst BCs. FST knockdown promoted the proliferation, migration and invasion of BT549 and HS578T cell lines. FST inhibited the apoptosis of mesenchymal cells by targeting BMP7.ConclusionsLow FST expression is associated with poor prognosis of patients with TNBC. FST expressions exhibit the anisotropic roles of apoptosis between mesenchymal and mesenchymal stem-like cells but promote the proliferation, migration, invasion in both of two subtypes of TNBC in vitro. FST may be a subtype-heterogeneous biomarker for monitoring the progress of TNBC.

Project description:BackgroundThe expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear.MethodsThe expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA).ResultsB7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p?<?0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression.ConclusionsOur data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.

Dataset Information

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance and Applications in Human Triple-Negative Breast Cancer.

Publications

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance and Applications in Human Triple-Negative Breast Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure