MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

/pdf/micrornas-new-biomarkers-for-diagnosis-prognosis-therapy-55egerjflf.pdf

MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

Cancer-associated fibroblasts (CAFs) are the major components of the tumor microenvironment. They may drive tumor progression, although the mechanisms involved are still poorly understood. Exosomes have emerged as important mediators of intercellular communication in cancer. They mediate horizontal transfer of microRNAs (miRs), mRNAs and proteins, thus affecting breast cancer progression. Differential expression profile analysis identified three miRs (miRs -21, -378e, and -143) increased in exosomes from CAFs as compared from normal fibroblasts. Immunofluorescence indicated that exosomes may be transferred from CAFs to breast cancer cells, releasing their cargo miRs. Breast cancer cells (BT549, MDA-MB-231, and T47D lines) exposed to CAF exosomes or transfected with those miRs exhibited a significant increased capacity to form mammospheres, increased stem cell and epithelial-mesenchymal transition (EMT) markers, and anchorage-independent cell growth. These effects were reverted by transfection with anti-miRs. Similarly to CAF exosomes, normal fibroblast exosomes transfected with miRs -21, -378e, and -143 promoted the stemness and EMT phenotype of breast cancer cells. Thus, we provided evidence for the first time of the role of CAF exosomes and their miRs in the induction of the stemness and EMT phenotype in different breast cancer cell lines. Indeed, CAFs strongly promote the development of an aggressive breast cancer cell phenotype.

/pdf/cancer-associated-fibroblasts-release-exosomal-micrornas-3s7milwpq3.pdf

Cancer-associated fibroblasts release exosomal microRNAs that dictate an aggressive phenotype in breast cancer

MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that have been found highly conserved among species. MiRNAs are able to negatively regulate gene expression through base pairing of 3’ UTRs of their target genes. Therefore, miRNAs have been shown to play an important role in regulating various cellular activities. Over the past decade, substantial evidences have been obtained to show that miRNAs are aberrantly expressed in human malignancies and could act as “OncomiRs” or “Tumor suppressor miRs”. In recent years, increasing number of studies have demonstrated the involvement of miRNAs in cancer metastasis. Many studies have shown that microRNAs could directly target genes playing a central role in epithelia-mesenchymal-transition (EMT), a cellular transformation process that allows cancer cells to acquire motility and invasiveness. EMT is considered an essential step driving the early phase of cancer metastasis. This review will summarize the recent findings and characterization of miRNAs that are involved in the regulation of EMT, migration, invasion and metastasis of cancer cells. Lastly, we will discuss potential use of miRNAs as diagnostic and prognostic biomarkers as well as therapeutic targets for cancer.

/pdf/regulation-of-cancer-metastasis-by-micrornas-4drcoi2yys.pdf

Regulation of cancer metastasis by microRNAs

Dysregulation of miRNA profile has been associated with a broad spectrum of cellular processes underlying progression of various human malignancies. Increasing evidence suggests that specific microRNA clusters might be of clinical utility, especially in triple-negative breast carcinoma (TNBC), devoid of both predictive markers and potential therapeutic targets. Here we provide a comprehensive review of the existing data on microRNAs in TNBC, their molecular targets, a putative role in invasive progression with a particular emphasis on the epithelial-to-mesenchymal transition (EMT) and acquisition of stem-cell properties (CSC), regarded both as prerequisites for metastasis, and significance for therapy. PubMed and Medline databases were systematically searched for the relevant literature. 121 articles have been selected and thoroughly analysed. Several miRNAs associated with EMT/CSC and invasion were identified as significantly (1) upregulated: miR-10b, miR-21, miR-29, miR-9, miR-221/222, miR-373 or (2) downregulated: miR-145, miR-199a-5p, miR-200 family, miR-203, miR-205 in TNBC. Dysregulation of miR-10b, miR-21, miR-29, miR-145, miR-200 family, miR-203, miR-221/222 was reported of prognostic value in TNBC patients. Available data suggest that specific microRNA clusters might play an important role in biology of TNBC, understanding of which should assist disease prognostication and therapy.

/pdf/micrornas-in-regulation-of-triple-negative-breast-cancer-poyrqyowo4.pdf

MicroRNAs in regulation of triple-negative breast cancer progression

The triple-negative breast cancer (TNBC), with a particularly poor prognosis, is increasingly recognized as heterogeneous in molecular signatures. MicroRNA expression profiles have been used for the classification and prognostication of breast cancer, numerous significantly upregulated microRNAs, i.e. miR-21, have been verified oncogenic in non-TNBCs. In present study, we determined the miR-21 levels in TNBC specimens, and TNBC cell levels in vitro, and then identified the role of miR-21 on tumor cell proliferation, apoptosis, and then identified PTEN as the possible target of the microRNA. It was shown that miR-21 expression is upregulated generally, and heterogeneous in TNBC specimens, posing a correlation with poor prognosis for TNBC patients. Further results demonstrated that the upregulated miR-21 promoted the tumor proliferation and inhibited cell apoptosis in vitro. And pro-apoptotic PTEN had been shown being targeted and downregulated. Therefore, our finding emphasized the oncogenic role of miR-21 in TNBC.

High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation

This study is to analyze the relationship between clinical parameters and prognosis and survival rates of breast cancer patients. A total of 1541 cases of breast cancer were retrospectively reviewed with respect to clinical parameters and the correlation with prognosis and survival rates. Among these patients, follow-up investigation was performed for 1381 cases. Clinical parameters including disease sites (the lesion quadrant), incidences, the number of axillary lymph node metastasis, maximum diameter of tumor, tumor regional lymph node metastasis (TNM) stages, pathological types were investigated. The estrogen receptor, progesterone receptor, Human Epidermal Growth Factor Receptor-2 levels were correlated with long term disease-free survival. Lymph node metastases, tumor diameter, TNM stage, and hormone receptor status are correlated with survival rates of breast cancer patients.

Factors related to survival rates for breast cancer patients.

To observe the radiotherapy sensitization effect of retroperitoneal lymph node metastasis in patients by sodium glycididazole in recent clinical efficacy and toxicity. A total of 42 patients admitted with metastasis and recurrence of retroperitoneal lymph node from September 2006 to December 2009 were classified with the method of case-control. After three dimensional conformal radiation therapy with or without sodium glycididazole (800 mg/m²) for sensitization, the results of recent clinical efficacy, relief of pain, and Karnofsky score were obtained. Tumor remission rate of patients in sensitization group (with sodium glycididazole) at post-radiotherapy 3 months was significant higher than that in control group (without sodium glycididazole) (52% vs. 24%; P<0.05). Oral dose of morphine daily, and Karnofsky score in anterior-posterior radiotherapy of patients in the sensitization group were significant different with those in the control group (93 ± 12 and 42 ± 6 mg vs. 94 ± 12 and 20 ± 5 mg and (65 ± 4) and (90 ± 9) vs. (64 ± 5) and (80 ± 10), respectively; P<0.01). Sodium glycididazole has positive radiotherapy sensitization to the metastasis or recurrence of retroperitoneal lymph node for digestive tract cancer, which could obviously improve the life quality or release the pain for patients.

Deguang Wang

Papers

High expression of miR-21 in triple-negative breast cancers was correlated with a poor prognosis and promoted tumor cell in vitro proliferation

Factors related to survival rates for breast cancer patients.

Study of the radiotherapy sensitizea-tion of retroperitoneal lymph node metastasis in patients by sodium glycididazole.