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McIntyre G, Jackson Z, Colina J, Sekhar S, DiFeo A. miR-181a: regulatory roles, cancer-associated signaling pathway disruptions, and therapeutic potential. Expert Opin Ther Targets 2024; 28:1061-1091. [PMID: 39648331 PMCID: PMC12054384 DOI: 10.1080/14728222.2024.2433687] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 11/20/2024] [Indexed: 12/10/2024]
Abstract
INTRODUCTION microRNA-181a (miR-181a) is a crucial post-transcriptional regulator of many mRNA transcripts and noncoding-RNAs, influencing cell proliferation, cancer cell stemness, apoptosis, and immune responses. Its abnormal expression is well-characterized in numerous cancers, establishing it as a significant genomic vulnerability and biomarker in cancer research. AREAS COVERED Here, we summarize miR-181a's correlation with poor patient outcomes across numerous cancers and the mechanisms governing miR-181a's activity and processing. We comprehensively describe miR-181a's involvement in multiple regulatory cancer signaling pathways, cellular processes, and the tumor microenvironment. We also discuss current therapeutic approaches to targeting miR-181a, highlighting their limitations and future potential. EXPERT OPINION miR-181a is a clinically relevant pan-cancer biomarker with potential as a therapeutic target. Its regulatory control of tumorigenic signaling pathways and immune responses positions it as a promising candidate for personalized treatments. The success of miR-181a as a target relies on the development of specific therapeutics platforms. Future research on miR-181a's role in the tumor microenvironment and the RNA binding proteins that regulate its stability will help uncover new techniques to targeting miR-181a. Further research into miR-181a serum levels in patients undergoing therapy will help to better stratify patients and enhance therapeutic success.
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Affiliation(s)
- Grace McIntyre
- Department of Pathology, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Zoe Jackson
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Jose Colina
- Department of Pathology, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Sreeja Sekhar
- Department of Pathology, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
| | - Analisa DiFeo
- Department of Pathology, Rackham Graduate School, University of Michigan, Ann Arbor, MI, USA
- Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA
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Rajput S, Sharma PK, Malviya R. Biomarkers and Treatment Strategies for Breast Cancer Recurrence. Curr Drug Targets 2023; 24:1209-1220. [PMID: 38164731 DOI: 10.2174/0113894501258059231103072025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2023] [Revised: 07/14/2023] [Accepted: 10/03/2023] [Indexed: 01/03/2024]
Abstract
Despite recent treatment advancements, breast cancer remains a life-threatening disease. Although treatment is successful in the early stages, a significant proportion of individuals with breast cancer eventually experience a recurrence of the disease. Breast tumour recurrence poses a significant medical issue. Despite tumours being a primary cause of mortality, there remains a limited understanding of the fundamental mechanisms underlying tumour recurrence. The majority of the time, after surgery or medical treatment, this metastatic disease manifests itself after the disease is undiagnosed for a considerable amount of time. This phenomenon is commonly referred to as a relapse or recurrence. Metastatic breast cancer has the potential to recur at varying intervals, ranging from a few months to several decades following the initial diagnosis and treatment. This article aimed to summarise the primary causes of breast cancer recurrence and highlight the key issues that need to be addressed in order to effectively decrease the mortality rate among breast cancer patients. This article discusses various therapeutic approaches currently employed and emerging treatment strategies that hold the potential for the complete cure of cancer.
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Affiliation(s)
- Shivam Rajput
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Pramod Kumar Sharma
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
| | - Rishabha Malviya
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, India
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Regulatory Interplay between miR-181a-5p and Estrogen Receptor Signaling Cascade in Breast Cancer. Cancers (Basel) 2021; 13:cancers13030543. [PMID: 33535487 PMCID: PMC7867078 DOI: 10.3390/cancers13030543] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Revised: 01/22/2021] [Accepted: 01/25/2021] [Indexed: 12/18/2022] Open
Abstract
Simple Summary Despite huge efforts in breast cancer care programs, patient’s survival rates greatly vary. Differences in response to therapy still represent the major challenge for clinicians and biologists. Define new anticancer mechanisms and innovative predictors for resistance could be a valid strategy to permanently defeat breast cancer. Here we propose the epigenetic based reprogramming of breast cancer, which leverages on the crosstalk between miR-181a-5p and Estrogen Receptor α. This simultaneously approach allows to induce miR-181a-5p and reduce the receptor expression, blocking the estrogen-dependent proliferative pathway underlying breast cancer progression. Since the epigenetic approach insists on transcriptional regulation, it is mostly independent of the acquired resistance mechanisms typically induced by prolonged endocrine therapy and therefore can be used as a sensitizer, neoadjuvant, or in combination with the standard in care treatments against breast cancer. Abstract The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.
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Ye P, Fang C, Zeng H, Shi Y, Pan Z, An N, He K, Zhang L, Long X. Differential microRNA expression profiles in tamoxifen-resistant human breast cancer cell lines induced by two methods. Oncol Lett 2018; 15:3532-3539. [PMID: 29467872 PMCID: PMC5796357 DOI: 10.3892/ol.2018.7768] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Accepted: 11/20/2017] [Indexed: 12/28/2022] Open
Abstract
Tamoxifen (TAM) resistance has become a severe problem for endocrine therapy of breast cancer. The present study investigated the association between microRNA (miRNA) expression and TAM resistance in breast cancer. The TAM-resistant breast cancer MCF-7C and MCF-7T cell lines were established using the human breast cancer cell line MCF-7 as the parental cell line and 4-hydroxytamoxifen (OHT) as the screening drug in vitro. The MCF-7C cell line was established by dose stepwise induction beginning with a low concentration of OHT; the MCF-7T cell line was established by temporal stepwise induction beginning with a high concentration of OHT. Differential miRNA expression profiles between TAM-sensitive (MCF-7) and TAM-resistant (MCF-7C and MCF-7T) breast cancer cell lines were detected and analyzed using RNA sequencing technology. The results of western blot analysis indicated that the level of ERα protein expression in drug-resistant cells was significantly increased. A total of 1,646 miRNAs were detected in all samples, including 1,376 known miRNAs and 270 predicted miRNAs. There were 118 miRNAs expressed at significantly different levels between MCF-7C and MCF-7 cells (P<0.05); among them, 67 miRNAs were upregulated (P<0.05) and 51 miRNA were downregulated (P<0.05). There were 42 miRNAs expressed at significantly different levels between MCF-7T and MCF-7 (P<0.05); among them, 23 miRNAs were upregulated (P<0.05) and 19 miRNAs were downregulated (P<0.05). There were 126 miRNAs with significant differences between MCF-7C and MCF-7T (P<0.05); among them, 76 miRNAs were upregulated (P<0.05) and 50 miRNAs were downregulated. On the basis of the results of the present study, we hypothesize that miR-21, miR-146a, miR-148a, miR-34a and miR-27a may serve important roles in mediating TAM resistance in breast cancer, and have potential as therapeutic targets for TAM-resistant breast cancer.
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Affiliation(s)
- Peng Ye
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Cheng Fang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Hui Zeng
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Yu Shi
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Zhongya Pan
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Nairui An
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Keli He
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Li Zhang
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
| | - Xinghua Long
- Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
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Identification of Recurrence-Related microRNAs from Bone Marrow in Hepatocellular Carcinoma Patients. J Clin Med 2015; 4:1600-11. [PMID: 26287250 PMCID: PMC4555079 DOI: 10.3390/jcm4081600] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 08/03/2015] [Accepted: 08/05/2015] [Indexed: 12/22/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is a poor-prognosis cancer due to its high rate of recurrence. microRNAs (miRNAs) are a class of small non-coding RNA molecules that affect crucial processes in cancer development. The objective of this study is to identify the role of miRNAs in patient bone marrow (BM) and explore the function of these molecules during HCC progression. We purified miRNAs from bone marrow cells of seven HCC patients, and divided them into three fractions by cell surface markers as follows: CD14(+) (macrophage), CD14(-)/CD45(+) (lymphocyte), and CD14(-)/CD45(-)/EpCAM(+) (epithelial cell). We employed microarray-based profiling to analyze miRNA expression in the bone marrow of patients with HCC. Differentially expressed miRNAs were significantly different between fractions from whole bone marrow, macrophages, and lymphocytes, and depended on stages in tumor progression. Differences in expression of miRNAs associated with cell proliferation also varied significantly between HCC patients with recurrence, multiple tumors, and advanced clinical stages. These results suggest that miRNA profiles in separated fractions of BM cells are associated with HCC progression.
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Sun Y, Yuan K, Zhang P, Ma R, Zhang QW, Tian XS. Crosstalk analysis of pathways in breast cancer using a network model based on overlapping differentially expressed genes. Exp Ther Med 2015; 10:743-748. [PMID: 26622386 DOI: 10.3892/etm.2015.2527] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Accepted: 05/07/2015] [Indexed: 12/30/2022] Open
Abstract
Multiple signal transduction pathways can affect each other considerably through crosstalk. However, the presence and extent of this phenomenon have not been rigorously studied. The aim of the present study was to identify strong and normal interactions between pathways in breast cancer and determine the main pathway. Five sets of breast cancer data were downloaded from the high-throughput Gene Expression Omnibus (GEO) and analyzed to identify differentially expressed (DE) genes using the Rank Product (RankProd) method. A list of pathways with differential expression was obtained by gene set enrichment analysis (GSEA) of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The DE genes that overlapped between pathways were identified and a crosstalk network diagram based on the overlap of DE genes was constructed. A total of 1,464 DE genes and 26 pathways were identified. In addition, the number of DE genes that overlapped between specific pathways were determined, and the greatest degree of overlap was between the extracellular matrix (ECM)-receptor interaction and Focal adhesion pathways, which had 22 overlapping DE genes. Weighted pathway analysis of the crosstalk between pathways identified that Pathways in cancer was the main pathway in breast cancer.
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Affiliation(s)
- Yong Sun
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China ; Department of General Surgery, Laiwu Hospital Affiliated to Taishan Medical College, Laiwu, Shandong 271100, P.R. China
| | - Kai Yuan
- Department of Breast Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, P.R. China
| | - Peng Zhang
- Department of General Surgery, Laiwu Hospital Affiliated to Taishan Medical College, Laiwu, Shandong 271100, P.R. China
| | - Rong Ma
- Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Qi-Wen Zhang
- Department of General Surgery, Laiwu Hospital Affiliated to Taishan Medical College, Laiwu, Shandong 271100, P.R. China
| | - Xing-Song Tian
- Department of Breast and Thyroid Surgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong 250021, P.R. China
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Sondermann A, Andreghetto FM, Moulatlet ACB, da Silva Victor E, de Castro MG, Nunes FD, Brandão LG, Severino P. MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer. Clin Exp Metastasis 2015; 32:521-30. [PMID: 26007293 DOI: 10.1007/s10585-015-9724-3] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 05/18/2015] [Indexed: 01/01/2023]
Abstract
Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.
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Affiliation(s)
- Adriana Sondermann
- Albert Einstein Research and Education Institute, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627, São Paulo, SP, 05652-000, Brazil
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Shinden Y, Iguchi T, Akiyoshi S, Ueo H, Ueda M, Hirata H, Sakimura S, Uchi R, Takano Y, Eguchi H, Sugimachi K, Kijima Y, Natsugoe S, Mimori K. miR-29b is an indicator of prognosis in breast cancer patients. Mol Clin Oncol 2015; 3:919-923. [PMID: 26171207 DOI: 10.3892/mco.2015.565] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2015] [Accepted: 03/31/2015] [Indexed: 12/12/2022] Open
Abstract
MicroRNA-29b (miR-29b) targets numerous important genes that mediate carcinogenesis and tumor development in breast cancer in vitro and in vivo. The aim of the present study was to determine the clinical significance of miR-29b expression in primary breast cancer patients. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) of miR-29b and certain target genes of miR-29b, such as DNA methyltransferase 3A (DNMT3A), ten-eleven translocation 1 (TET1) and thymine DNA glycosylase (TDG), was performed in 94 primary breast cancer samples. Low expression of miR-29b in primary tumors was significantly associated with poorer disease-free survival (DFS) (P=0.0075) and overall survival (OS) (p=0.0012). Multivariate analysis indicated that miR-29b expression was an independent prognostic factor for OS [relative risk=15.6 (2.33-348), P=0.0026]. In addition, a significant inverse correlation was identified between the expression levels of DNMT3A and miR-29b in estrogen receptor-positive breast cancer patients (P=0.027). To the best of our knowledge, this is the first study to investigate the clinicopathological significance of miR-29b in breast cancer cases and miR-29b is shown to act as a tumor suppressive microRNA in breast cancer and as a potential marker for recurrence and metastasis in breast cancer patients.
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Affiliation(s)
- Yoshiaki Shinden
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan ; Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890-8520, Japan
| | - Tomohiro Iguchi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Sayuri Akiyoshi
- National Hospital Organization Kyushu Cancer Center, Fukuoka, Fukuoka 811-1395, Japan
| | - Hiroki Ueo
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Masami Ueda
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Hidenari Hirata
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Shotaro Sakimura
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Ryutaro Uchi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Yuki Takano
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Hidetoshi Eguchi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Keishi Sugimachi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
| | - Yuko Kijima
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890-8520, Japan
| | - Shoji Natsugoe
- Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Kagoshima 890-8520, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita 874-0838, Japan
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Prediction of poor prognosis in breast cancer patients based on microRNA-21 expression: a meta-analysis. PLoS One 2015; 10:e0118647. [PMID: 25706383 PMCID: PMC4338069 DOI: 10.1371/journal.pone.0118647] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2014] [Accepted: 01/07/2015] [Indexed: 12/21/2022] Open
Abstract
Background MicroRNA-21 (miRNA-21 or miR-21) may act as a prognostic biomarker of cancer. However, the available evidence is controversial. Therefore, the present meta-analysis summarizes this evidence and evaluates the prognostic role of this gene in breast cancer. Methods The meta-analysis was conducted by searching the databases of PubMed, EMBASE, Web of Science and Chinese database-China National Knowledge Infrastructure (CNKI). Data were extracted from studies that investigated the association between miR-21 expression and survival outcomes in breast cancer patients. With respect to survival outcomes, the pooled hazard ratios (HRs) of miR-21 were calculated given a 95% confidence interval (CI). Results Our meta-analysis identified a total of 10 studies involving 1,439 cases. Further investigation demonstrated that a high miR-21 expression can predict poor overall survival (OS) (HR = 2.57, 95% CI: 1.37—4.81, P = 0.003) and shortened disease-free/recurrence-free survival (DFS/RFS) (HR = 1.45, 95% CI: 1.16—1.82, P = 0.001) in breast cancer patients. Moreover, high miR-21 expression was significantly correlated with lowered OS in the Asian group (HR = 5.07, 95% CI: 2.89—8.92, P < 0.001), but not in the Caucasian cohort (HR = 1.44, 95% CI: 0.99—2.10, P = 0.058). Furthermore, odds ratios (ORs) showed that up-regulated miR-21 levels were associated with multiple clinical characteristics. Conclusion Our results indicated that miR-21 can predict unfavorable prognoses in breast cancer patients, especially in Asians.
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Liao W, Liu X, Peng H, Xu L. [The expression and functional study of miR-181a in pediatric acute lymphoblastic leukemia]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2015; 36:53-7. [PMID: 25641148 PMCID: PMC7343040 DOI: 10.3760/cma.j.issn.0253-2727.2015.01.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Indexed: 12/19/2022]
Abstract
OBJECTIVE To investigate the expression of miR-181a in bone marrow (BM) samples of pediatric acute lymphoblastic leukemia (ALL) and explore the mechanism of miR-181a on ALL cell line CCRF-CEM and drug resistance cell line CEM-C1. METHODS BM samples were obtained from 18 patients where matched samples at initial diagnosis and first BM relapse or complete remission were available. BM samples and cord blood samples (normal controls) were used to confirm the differential expression of miRNA-181a by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of miR-181a in both CCRF-CEM and its mutidrug-resistant counterpart CEM-C1 cells were also detected. Then, CCK-8 assay was performed to quantify the effects of miR-181a on CEM-C1 and CCRF-CEM cells growth and viability. RESULTS Up-regulated miR-181a with higher fold changes in both initial diagnosis (4.84 ± 2.71, 7.58 ± 2.50) and relapsed samples (6.53 ± 2.20) compared to normal controls (1.41 ± 0.53) (P=0.017, 0.000, 0.001, respectively) were observed, whereas the miR-181a expression in the samples of CR (1.35 ± 0.35) compared to normal control showed no significant difference (P=0.863). The miR-181a expression level was higher in CEM-C1 cells (-4.39 ± 0.08) than of in CCRF-CEM cells (-2.32 ± 0.03) (P=0.000). CCK-8 assay revealed that suppression of miR-181a in CEM-C1 cells by transfecting the specific inhibitor of miR-181a led to significantly higher cellular proliferation inhibition rate than negative control cells (P<0.05), IC50 were 30.61 ng/ml and 2 255.00 ng/ml with RI as 73.67. While increased miR-181a in CCRF-CEM cells led to significantly lower CPIR than negative control cells (P<0.01), IC50 were 126.60 ng/ml and 1.34 ng/ml with RI as 94.26. CONCLUSION Upregulation of miR-181a might play an important role in the development of drug resistance in CEM-C1 cells, and knockdown of miR-181a could sensitize CEM-C1 cells to camptothecin; Meanwhile increased expression of miR-181a could promote CCRF-CEM drug resistance. These results suggested that suppression of miR-181a expression might provide a promising therapeutic in drug resistance of leukaemia.
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Affiliation(s)
- Wang Liao
- Birth Cohort Study Lab, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Xiaodan Liu
- Birth Cohort Study Lab, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Hongxia Peng
- Birth Cohort Study Lab, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou 510623, China
| | - Ling Xu
- Birth Cohort Study Lab, Guangzhou Women and Children Medical Center, Guangzhou Medical University, Guangzhou 510623, China
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MacKenzie TA, Schwartz GN, Calderone HM, Graveel CR, Winn ME, Hostetter G, Wells WA, Sempere LF. Stromal expression of miR-21 identifies high-risk group in triple-negative breast cancer. THE AMERICAN JOURNAL OF PATHOLOGY 2014; 184:3217-25. [PMID: 25440114 DOI: 10.1016/j.ajpath.2014.08.020] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 08/19/2014] [Indexed: 01/09/2023]
Abstract
Triple-negative breast cancer (TNBC) is an aggressive subtype defined by the lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. Expression of miR-21, an oncomiR, is frequently altered and may be distinctly expressed in the tumor stroma. Because tumor lesions are a complex mixture of cell types, we hypothesized that analysis of miR-21 expression at single-cell resolution could provide more accurate information to assess disease recurrence risk and BC-related death. We implemented a fully automated, tissue slide-based assay to detect miR-21 expression in 988 patients with BC. The miR-21(High) group exhibited shorter recurrence-free survival [hazard ratio (HR), 1.71; P < 0.001] and BC-specific survival (HR, 1.96; P < 0.001) in multivariate regression analyses. When tumor compartment and levels of miR-21 expression were considered, significant associations with poor clinical outcome were detected exclusively in tumor epithelia from estrogen receptor- and/or progesterone receptor-positive human epidermal growth factor receptor 2-negative cases [recurrence-free survival: HR, 3.67 (P = 0.006); BC-specific survival: HR, 5.13 (P = 0.002)] and in tumor stroma from TNBC cases [recurrence-free survival: HR, 2.59 (P = 0.013); BC-specific survival: HR, 3.37 (P = 0.003)]. These findings suggest that the context of altered miR-21 expression provides clinically relevant information. Importantly, miR-21 expression was predominantly up-regulated and potentially prognostic in the tumor stroma of TNBC.
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Affiliation(s)
- Todd A MacKenzie
- Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Gary N Schwartz
- Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Heather M Calderone
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan
| | - Carrie R Graveel
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan
| | - Mary E Winn
- Bioinformatics and Biostatistics Core, Van Andel Research Institute, Grand Rapids, Michigan
| | - Galen Hostetter
- Laboratory of Analytical Pathology, Van Andel Research Institute, Grand Rapids, Michigan
| | - Wendy A Wells
- Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
| | - Lorenzo F Sempere
- Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan; Laboratory of microRNA Diagnostics and Therapeutics, Van Andel Research Institute, Grand Rapids, Michigan.
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Alečković M, Kang Y. Regulation of cancer metastasis by cell-free miRNAs. Biochim Biophys Acta Rev Cancer 2014; 1855:24-42. [PMID: 25450578 DOI: 10.1016/j.bbcan.2014.10.005] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2014] [Accepted: 10/17/2014] [Indexed: 02/08/2023]
Abstract
MicroRNAs (miRNAs) are integral molecules in the regulation of numerous physiological cellular processes that have emerged as critical players in cancer initiation and metastatic progression, both by promoting and suppressing metastasis. Recently, cell-free miRNAs shed from cancer cells into circulation have been reported in cancer patients, raising hope for development of novel biomarkers that can be routinely measured in easily accessible samples. In fact, establishing miRNA expression in the circulation likely has advantages over determination in primary tumor tissue, further augmenting the potential applications of miRNA detection in oncological practice. In addition, secretion of miRNAs impacting distant cell signaling or promoting the formation of a niche that sustains a distant tumor microenvironment allows for new treatment approaches to thwart cancer progression.
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Affiliation(s)
- Maša Alečković
- Department of Molecular Biology, Princeton University, Princeton NJ 08544, USA
| | - Yibin Kang
- Department of Molecular Biology, Princeton University, Princeton NJ 08544, USA.
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14
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Xue J, Niu J, Wu J, Wu ZH. MicroRNAs in cancer therapeutic response: Friend and foe. World J Clin Oncol 2014; 5:730-743. [PMID: 25302173 PMCID: PMC4129536 DOI: 10.5306/wjco.v5.i4.730] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2014] [Revised: 03/15/2014] [Accepted: 06/18/2014] [Indexed: 02/06/2023] Open
Abstract
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, microRNAs (miRNAs), a class of non-coding 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 miRNAs is to post-transcriptionally regulate gene expression depending on recognition of complementary sequence residing in target mRNAs. Commonly, a particular miRNA recognition sequence could be found in a number of genes, which allows a single miRNA to regulate multiple functionally connected genes simultaneously and/or chronologically. Furthermore, a single gene can be targeted and regulated by multiple miRNAs. However, previous studies have demonstrated that miRNA 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 miRNA. Here we summarize recent progress in studies on miRNA function in cancer initiation, metastasis and therapeutic response, focusing on breast cancer. The varying functions of miRNAs and potential application of using miRNAs as biomarkers as well as therapeutic approaches are further discussed in the context of different cancers.
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15
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Zhou X, Wang X, Huang Z, Wang J, Zhu W, Shu Y, Liu P. Prognostic value of miR-21 in various cancers: an updating meta-analysis. PLoS One 2014; 9:e102413. [PMID: 25019505 PMCID: PMC4097394 DOI: 10.1371/journal.pone.0102413] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2014] [Accepted: 06/17/2014] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. METHODS We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). RESULTS The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66-2.19) for OS, 1.42 (95% CI: 1.16-1.74) for DFS and 2.2 (95% CI: 1.64-2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18-4.9) for OS. CONCLUSIONS Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical.
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Affiliation(s)
- Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiaping Wang
- Key Laboratory of Human Functional Genomics of Jiangsu Province, Clinical Diabetes Centre of Jiangsu Province, Nanjing Medical University, Nanjing, China
| | - Zebo Huang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Wang
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wei Zhu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- * E-mail: (PL); (WZ)
| | - Yongqian Shu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Cancer Center of Nanjing Medical University, Nanjing, China
| | - Ping Liu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Cancer Center of Nanjing Medical University, Nanjing, China
- * E-mail: (PL); (WZ)
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16
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Browne G, Taipaleenmäki H, Stein GS, Stein JL, Lian JB. MicroRNAs in the control of metastatic bone disease. Trends Endocrinol Metab 2014; 25:320-7. [PMID: 24811921 PMCID: PMC4075094 DOI: 10.1016/j.tem.2014.03.014] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2014] [Revised: 03/21/2014] [Accepted: 03/25/2014] [Indexed: 02/08/2023]
Abstract
Bone metastasis is a common and devastating complication of late-stage breast and prostate cancer. Complex interactions between tumor cells, bone cells, and a milieu of components in their microenvironment contribute to the osteolytic, osteoblastic, or mixed lesions present in patients with metastasis to bone. In the past decade microRNAs (miRNAs) have emerged as key players in cancer progression, but the importance of miRNAs in regulating cancer metastasis to bone is only now being appreciated. We emphasize here important concepts of bone biology and miRNAs in the context of breast and prostate cancer, and focus on recent advances that have improved our understanding of the role of specific miRNAs with direct involvement in metastatic bone disease.
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Affiliation(s)
- Gillian Browne
- Vermont Cancer Center and Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT, 05405, USA
| | - Hanna Taipaleenmäki
- Heisenberg-Group for Molecular Skeletal Biology, Department of Trauma, Hand and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Gary S Stein
- Vermont Cancer Center and Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT, 05405, USA
| | - Janet L Stein
- Vermont Cancer Center and Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT, 05405, USA
| | - Jane B Lian
- Vermont Cancer Center and Department of Biochemistry, University of Vermont College of Medicine, Burlington, VT, 05405, USA.
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17
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Wang J, Zhang KY, Liu SM, Sen S. Tumor-associated circulating microRNAs as biomarkers of cancer. Molecules 2014; 19:1912-1938. [PMID: 24518808 PMCID: PMC6271223 DOI: 10.3390/molecules19021912] [Citation(s) in RCA: 114] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Revised: 01/24/2014] [Accepted: 01/29/2014] [Indexed: 02/06/2023] Open
Abstract
MicroRNAs (miRNAs), the 17- to 25-nucleotide long noncoding RNAs that modulate the expression of mRNAs and proteins, have emerged as critical players in cancer initiation and progression processes. Deregulation of tissue miRNA expression levels associated with specific genetic alterations has been demonstrated in cancer, where miRNAs function either as oncogenes or as tumor-suppressor genes and are shed from cancer cells into circulation. The present review summarizes and evaluates recent advances in our understanding of the characteristics of tumor tissue miRNAs, circulating miRNAs, and the stability of miRNAs in tissues and their varying expression profiles in circulating tumor cells, and body fluids including blood plasma. These advances in knowledge have led to intense efforts towards discovery and validation of differentially expressing tumor-associated miRNAs as biomarkers and therapeutic targets of cancer. The development of tumor-specific miRNA signatures as cancer biomarkers detectable in malignant cells and body fluids should help with early detection and more effective therapeutic intervention for individual patients.
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Affiliation(s)
- Jin Wang
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ke-Yong Zhang
- Department of orthopedics, Daye People's Hospital, Daye, Hubei 435100, China
| | - Song-Mei Liu
- Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China
| | - Subrata Sen
- Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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18
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Godfrey AC, Xu Z, Weinberg CR, Getts RC, Wade PA, DeRoo LA, Sandler DP, Taylor JA. Serum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort. Breast Cancer Res 2013; 15:R42. [PMID: 23705859 PMCID: PMC3706791 DOI: 10.1186/bcr3428] [Citation(s) in RCA: 90] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 05/24/2013] [Indexed: 12/17/2022] Open
Abstract
Introduction MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis. Methods We used Affymetrix arrays to examine serum miRNA expression profiles in 410 participants in the Sister Study, a prospective cohort study of 50,884 women. All women in the cohort had never been diagnosed with breast cancer at the time of enrollment. We compared global miRNA expression patterns in 205 women who subsequently developed breast cancer and 205 women who remained breast cancer-free. In addition within the case group we examined the association of miRNA expression in serum with different tumor characteristics, including hormone status (ER, PR, and HER-2) and lymph node status. Results Overall, 414 of 1,105 of the human miRNAs on the chip were expressed above background levels in 50 or more women. When the average expression among controls was compared to cases using conditional logistic regression, 21 miRNAs were found to be differentially expressed (P≤.05). Using qRT-PCR on a small, independent sample of 5 cases and 5 controls we verified overexpression of the 3 highest expressing miRNAs among cases, miR-18a, miR-181a, and miR-222; the differences were not statistically significant in this small set. The 21 differentially expressed miRNAs are known to target at least 82 genes; using the gene list for pathway analysis we found enrichment of genes involved in cancer-related processes. In a separate case-case analyses restricted to the 21 miRNAs, we found 7 miRNAs with differential expression for women whose breast tumors differed by HER-2 expression, and 10 miRNAs with differential expression by nodal status. Conclusions miRNA levels in serum show a number of small differences between women who later develop cancer versus those who remain cancer-free.
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Lin S, Pan L, Guo S, Wu J, Jin L, Wang JC, Wang S. Prognostic role of microRNA-181a/b in hematological malignancies: a meta-analysis. PLoS One 2013; 8:e59532. [PMID: 23533632 PMCID: PMC3606212 DOI: 10.1371/journal.pone.0059532] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2013] [Accepted: 02/15/2013] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes, and have prognostic value for patients with cancers. In recent years, the miR-181 family was found dysregulated in a variety of human cancers and significantly associated with clinical outcome of cancerous patients. MiR-181a and miR-181b (miR-181a/b) were the most investigated members in the family. However, the results of miR-181a/b from different studies were inconsistent. Therefore, we performed a meta-analysis to summarize all the results from available studies, aiming to delineate the prognostic role of miR-181a/b in human cancers. METHODS The identified articles were retrieved from the two main on-line databases, PubMed and EMBASE. We extracted and estimated the hazard ratios (HRs) for overall survival (OS), which compared the high and low expression levels of miR-181a/b in patients of the available studies. Each individual HR was used to calculate the pooled HR. RESULTS Eleven studies of 1252 patients were selected into the final meta-analysis after a strict filtering and qualifying process. Fixed model or random model method was chosen depending on the heterogeneity between the studies. The subgroup analysis showed that high expressed miR-181a/b could prolong OS in patients with hematological malignancies rather than low expression level (HR = 0.717, P<0.0001). But the expression of miR-181a/b was not significantly relative to OS in patients with various cancers (HR = 0.861, p = 0.356). CONCLUSION Our study indicates that the expression level of miR-181a/b is significantly associated with OS in hematological malignancies and can be an important clinical prognostic factor for those patients.
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Affiliation(s)
- Shenglong Lin
- Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Lili Pan
- Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
| | - Shicheng Guo
- National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Junjie Wu
- National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai, China
| | - Li Jin
- National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Jiu-Cun Wang
- National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
| | - Shaoyuan Wang
- Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian Province, China
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20
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Pathways to breast cancer recurrence. ISRN ONCOLOGY 2013; 2013:290568. [PMID: 23533807 PMCID: PMC3603357 DOI: 10.1155/2013/290568] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 01/17/2013] [Indexed: 12/22/2022]
Abstract
Breast cancer remains a deadly disease, even with all the recent technological advancements. Early intervention has made an impact, but an overwhelmingly large number of breast cancer patients still live under the fear of “recurrent” disease. Breast cancer recurrence is clinically a huge problem and one that is largely not well understood. Over the years, a number of factors have been studied with an overarching aim of being able to prognose recurrent disease. This paper attempts to provide an overview of our current knowledge of breast cancer recurrence and its associated challenges. Through a survey of the literature on cancer stem cells (CSCs), epithelial-mesenchymal transition (EMT), various signaling pathways such as Notch/Wnt/hedgehog, and microRNAs (miRNAs), we also examine the hypotheses that are currently under investigation for the prevention of breast cancer recurrence.
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21
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Sempere LF. Integrating contextual miRNA and protein signatures for diagnostic and treatment decisions in cancer. Expert Rev Mol Diagn 2012; 11:813-27. [PMID: 22022944 DOI: 10.1586/erm.11.69] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed.
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Affiliation(s)
- Lorenzo F Sempere
- Department of Medicine, Rubin 763 HB7936, Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, NH 03756-1000, USA.
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22
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Rhodes LV, Tilghman SL, Boue SM, Wang S, Khalili H, Muir SE, Bratton MR, Zhang Q, Wang G, Burow ME, Collins-Burow BM. Glyceollins as novel targeted therapeutic for the treatment of triple-negative breast cancer. Oncol Lett 2011; 3:163-171. [PMID: 22740874 DOI: 10.3892/ol.2011.460] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2011] [Accepted: 09/21/2011] [Indexed: 12/14/2022] Open
Abstract
The purpose of this study was to investigate the effects of glyceollins on the suppression of tumorigenesis in triple-negative breast carcinoma cell lines. We further explored the effects of glyceollins on microRNA and protein expression in MDA-MB-231 cells. Triple-negative (ER-, PgR- and Her2/neu-) breast carcinoma cells were used to test the effects of glyceollins on tumorigenesis in vivo. Following this procedure, unbiased microarray analysis of microRNA expression was performed. Additionally, we examined the changes in the proteome induced by glyceollins in the MDA-MB-231 cells. Tumorigenesis studies revealed a modest suppression of MDA-MB-231 and MDA-MB-468 cell tumor growth in vivo. In response to glyceollins we observed a distinct change in microRNA expression profiles and proteomes of the triple-negative breast carcinoma cell line, MDA-MB-231. Our results demonstrated that the glyceollins, previously described as anti-estrogenic agents, also exert antitumor activity in triple-negative breast carcinoma cell systems. This activity correlates with the glyceollin alteration of microRNA and proteomic expression profiles.
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Affiliation(s)
- Lyndsay V Rhodes
- Department of Medicine, Section of Hematology and Medical Oncology, New Orleans, LA 70125, USA
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