miR-185 Suppresses Tumor Proliferation by Directly Targeting E2F6 and DNMT1 and Indirectly Upregulating BRCA1 in Triple-Negative Breast Cancer

Tang, Hailin; Liu, Peng; Yang, Lu; Feng, Yali; Wu, Peng; Li, Xiaoping; Chen, Bin; Zhang, Lijuan; Xie, Xiaoming

doi:10.1158/1535-7163.mct-14-0243

Cited by 100 publications

(64 citation statements)

References 54 publications

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“…miRNAs play a vital role in many crucial cellular processes, including apoptosis, differentiation, invasion, and proliferation (32)(33)(34). The abnormal expression of miRNA has been reported in many cancers, including breast (35), gastric (36), colorectal (37), and liver cancers (38), as well as leukemia (39) and lymphoma (40). miR-124 has been described as a brain-specific miRNA in mammals, and may play a role in defining and maintaining neuron-specific characteristics (41,42).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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Abstract. MicroRNA (miRNA) is a type of endogenous non-coding RNA implicated in various cellular processes. Studies have shown that miR-124 is involved in the malignant progression of cancer, but little is known concerning its potential role in breast cancer. Therefore, the purpose of this study was to conduct a functional analysis of miR-124 in breast cancer, and to identify its target genes in this disease. To this end, we used quantitative real-time PCR to examine the expression level of miR-124 in breast cancer tissue specimens and cell lines. To study the functional significance of miR-124, we overexpressed miR-124 with miR-124 mimics and observed breast cancer cell proliferation, colony formation, migration, and invasion abilities by in vitro cell culture experiments. Target prediction algorithms and luciferase reporter gene assays were used to identify the target genes of miR-124. We also knocked down miR-124 targets using short hairpin RNA (shRNA) constructs, and observed associated breast cancer cell characteristics by in vitro cell culture experiments. We found that miR-124 expression significantly decreased in breast cancer tissues and cells compared to normal tissues and cells. In addition, cell proliferation, colony formation, migration, and invasion were decreased after overexpression of miR-124 in breast cancer cells. Furthermore, we used several algorithms to identify the snail family zinc finger 2 (SNAI2) as a potential target gene of miR-124. The protein expression level and luciferase activity of the 3'-untranslated region of SNAI2 were significantly decreased in breast cancer cells transfected with miR-124 mimics. Cell proliferation, colony formation, migration, and invasion were also decreased after knockdown of SNAI2 by shRNA. In conclusion, our data suggest that miR-124 expression is decreased in breast cancer and plays an important role as a tumor suppressor gene by targeting SNAI2. These findings may reveal novel perspectives for clinical treatments against breast cancer.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Sun

et al. 2016

Oncology Reports

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“…Moreover, some tumor-suppressor miRNAs inhibit oncogenic transcription factors, including Myc (let-7 b, 7 c and 7 d) [78], B-cell CLL/lymphoma 6 (BCL6, mir-127-3p) [85], v-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1, mir-125 a, miR-125 b) [84], v-ets avian erythroblastosis virus E26 oncogene homolog 2 (ETS2, mir-320) [102], SRY box 9, (SOX9, miR-140) [86] and E2F transcription factor 6 (E2F6, miR-185) [95], all of which were found to be downregulated in DCIS (Table 1). During the tumorigenic transformation process, premalignant breast epithelial cells lose cell polarity and gain deregulated proliferation, leading to rapid growth and formation of the tumor mass.…”

Section: Mirnas Downregulated In Dcismentioning

confidence: 99%

“…Some of the miRNAs downregulated in DCIS are implicated in the downregulation of anti-apoptotic factors, including BCL2 (miR-143, miR195) [88,99,123], Survivin (miR-143) [89], Bcl-w (miR-497) [105] and 14-3-3f (miR-451) [103] (Table 1). In addition, these identified tumor-suppressive miRNAs also functionally target other biological processes including cell-cycle progression (Cyclin D1, targeted by miR-143) [89], angiogenesis (vascular endothelial growth factor A [VEGFA], targeted by miR-145 and miR-185) [91,96], epigenetic regulation (TET1-3, targeted by miR-22; DNA (cytosine-5)-methyltransferase 1 [DNMT1], targeted by miR-185) [79,95], Rho-dependent signal transduction (RTKN, targeted by miR-145) [92], invasion (ADP ribosylation factor 6 [ARF6], targeted by miR-145; CD147, targeted by miR-22; Six1, targeted by miR-204; Smad3, targeted by miR-489) [80,93,100,104] and degradation of the extracellular matrix (ECM) (urokinase plasminogen activator, uPA, targeted by miR-193 b) [97] (Table 1).…”

Section: Mirnas Downregulated In Dcismentioning

confidence: 99%

Noncoding RNAs in breast cancer

Lo¹,

Wolfson²,

Zhou³

et al. 2015

Briefings in Functional Genomics

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The mammalian transcriptome has recently been revealed to encompass a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. MicroRNAs (miRNAs), the best studied of the short noncoding RNAs (sncRNAs), have been extensively characterized with regard to their biogenesis, function and importance in tumorigenesis. Another class of sncRNAs called piwi-interacting RNAs (piRNAs) has also gained attention recently in cancer research owing to their critical role in stem cell regulation. Long noncoding RNAs (lncRNAs) of >200 nucleotides in length have recently emerged as key regulators of developmental processes, including mammary gland development. lncRNA dysregulation has also been implicated in the development of various cancers, including breast cancer. In this review, we describe and discuss the roles of sncRNAs (including miRNAs and piRNAs) and lncRNAs in the initiation and progression of breast tumorigenesis, with a focus on outlining the molecular mechanisms of oncogenic and tumor-suppressor ncRNAs. Moreover, the current and potential future applications of ncRNAs to clinical breast cancer research are also discussed, with an emphasis on ncRNA-based diagnosis, prognosis and future therapeutics.

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“…Each type of miRNA may modulate the expression of numerous mRNAs simultaneously; therefore, miRNAs serve critical roles in biological functions, including cell proliferation, cell cycle progression, migration, invasion, metastasis, apoptosis, metabolism and the immune response (12)(13)(14)(15)(16)(17)(18). Accumulating studies have indicated that there are associations between miRNA expression and the clinical features of patients with cancer, including tumor size, tumor-node-metastasis (TNM) stage, development, survival time, disease recurrence and metastasis (19)(20)(21)(22). miRNAs have been reported to be frequently dysregulated in various types of human cancer, and may function as tumor suppressors or oncogenes in tumorigenesis and tumor development (23).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-215 acts as a tumor suppressor in breast cancer by targeting AKT serine/threonine kinase 1

et al. 2017

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Abstract. There are accumulating reports that microRNAs are dysregulated in a number of human cancer types, and that they may function as tumor suppressors or oncogenes in tumorigenesis and tumor development. microRNA-215 (miR-215) has been identified as a tumor suppressor in epithelial ovarian, pancreatic, non-small cell lung and colon cancer, whereas it may act as an oncogene in gastric and cervical cancer. The role of miR-215 in breast cancer carcinogenesis and progression has yet to be elucidated. In the present study, the expression level of miR-215 was determined in breast cancer tissues and cell lines using the reverse transcription-quantitative polymerase chain reaction. The effects of miR-215 overexpression on proliferation and the invasive capacity of breast cancer cells were assessed using MTT and cell invasion assays. The results revealed that miR-215 was significantly downregulated in breast cancer tissues and cell lines. Restoration of miR-215 expression inhibited the proliferation and invasion of breast cancer cells. The underlying molecular mechanism for the suppression of proliferation and invasion by miR-215 was investigated. AKT serine/threonine kinase 1 (AKT1) was validated as a novel direct target of miR-215, and the effect of AKT1 small interfering RNA mimicked the effect of miR-215 overexpression in breast cancer cells. These results indicated that miR-215 acted as a tumor suppressor, and that its downregulation in tumor tissues may contribute to the carcinogenesis and progression of breast cancer, indicating that miR-215 may be a novel therapeutic target for the treatment of breast cancer.

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miR-185 Suppresses Tumor Proliferation by Directly Targeting E2F6 and DNMT1 and Indirectly Upregulating BRCA1 in Triple-Negative Breast Cancer

Cited by 100 publications

References 54 publications

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

MicroRNA-124 inhibits cell proliferation and migration by regulating SNAI2 in breast cancer

Noncoding RNAs in breast cancer

MicroRNA-215 acts as a tumor suppressor in breast cancer by targeting AKT serine/threonine kinase 1

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