MiRNA expression in urothelial carcinomas: Important roles of miR‐10a, miR‐222, miR‐125b, miR‐7 and miR‐452 for tumor stage and metastasis, and frequent homozygous losses of miR‐31

Veerla, Srinivas; Lindgren, David; Kvist, Anders; Frigyesi, Attila; Staaf, Johan; Persson, Helena; Liedberg, Fredrik; Chebil, Gunilla; Guðjónsson, Sigurður; Borg, Åke; Månsson, Wiking; Rovira, Carlos; Höglund, Mattias

doi:10.1002/ijc.24183

Cited by 206 publications

(164 citation statements)

References 50 publications

(52 reference statements)

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“…20 In our study, preferential adhesion of HEC1A cells to fibronectin and laminin can be accounted by the binding of cell surface molecules with these 2 ECM proteins as an initial step of cancer cell invasion and metastasis. 21,22 Taken together, our results implied that miR-7, miR-194 and miR449b knockdown and miR-204 induction may suppress cell motility by hindering adhesion to fibronectin-/lamininbearing surfaces.…”

Section: Cancer Cell Biologymentioning

confidence: 70%

“…MicroRNAs (miRNAs) are small noncoding RNA molecules of [19][20][21][22][23][24] nucleotides that regulate gene expression posttranscriptionally through imperfect base pairing with the 3 0 -untranslated region (3 0 UTR) of target mRNAs, causing transcript degradation and translational inhibition. 3 Approximately 20-30% of all genes are targeted by miRNAs and a single miRNA may target as many as 200 genes.…”

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confidence: 99%

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Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Chung

Lau

Cheung

et al. 2011

Intl Journal of Cancer

152

128

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TXMicroRNAs (miRNAs) regulate mRNA stability and protein expression, and certain miRNAs have been demonstrated to act either as oncogenes or tumor suppressors. Differential miRNA expression signatures have been documented in many human cancers but the role of miRNAs in endometrioid endometrial cancer (EEC) remains poorly understood. This study identifies significantly dysregulated miRNAs of EEC cells, and characterizes their impact on the malignant phenotype. We studied the expression of 365 human miRNAs using Taqman low density arrays in EECs and normal endometriums. Candidate differentially expressed miRNAs were validated by quantitative real-time PCR. Expression of highly dysregulated miRNAs was examined in vitro through the effect of anti-/pre-miRNA transfection on the malignant phenotype. We identified 16 significantly dysregulated miRNAs in EEC and 7 of these are novel findings with respect to EEC. Antagonizing the function of miR-7, miR-194 and miR-449b, or overexpressing miR-204, repressed migration, invasion and extracellular matrix-adhesion in HEC1A endometrial cancer cells. FOXC1 was determined as a target gene of miR-204, and two binding sites in the 3 0 -untranslated region were validated by dual luciferase reporter assay. FOXC1 expression was inversely related to miR-204 expression in EEC. Functional analysis revealed the involvement of FOXC1 in migration and invasion of HEC1A cells. Our results present dysfunctional miRNAs in endometrial cancer and identify a crucial role for miR-204-FOXC1 interaction in endometrial cancer progression. This miRNA signature offers a potential biomarker for predicting EEC outcomes, and targeting of these cancer progression-and metastasis-related miRNAs offers a novel potential therapeutic strategy for the disease.Endometrial cancer is a common cause of gynecological cancer death. The most dominant subtype, endometrioid endometrial cancer (EEC), accounts for >80% of this cancer. Menopause and unopposed estrogenic stimulation are typical risk factors. Patients are generally treated with surgery, radiation, chemotherapy or hormone therapy. Patients with early stage disease have 5-year survival rates over 80%, however, about 15-20% develop metastasis. 1 These patients and those with advanced stage disease or recurrence have poor prognosis due to limitation of effective treatment. 2 Understanding the pathogenesis of this disease may provide insights for the development of novel therapeutic strategies.MicroRNAs (miRNAs) are small noncoding RNA molecules of 19-24 nucleotides that regulate gene expression posttranscriptionally through imperfect base pairing with the 3 0 -untranslated region (3 0 UTR) of target mRNAs, causing transcript degradation and translational inhibition. 3 Approximately 20-30% of all genes are targeted by miRNAs and a single miRNA may target as many as 200 genes. 4 In human cancers, >50% of the miRNA genes are located in chromosomal fragile sites, minimal regions containing loss of heterozygosity, minimal amplicons or common breakpoint regions. 5 DNA ...

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Section: Cancer Cell Biologymentioning

confidence: 70%

mentioning

confidence: 99%

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Chung

Lau

Cheung

et al. 2011

Intl Journal of Cancer

152

128

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“…They are identical at nucleotides 2-8, which seems to be the most important segment for target recognition (51). miR10a has been studied in several tumors (52)(53)(54). According to TargetScan4.0 analysis, the KLF4 mRNA target site for miR10b overlaps with miR-10a.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Tian

Luo

Cai

et al. 2010

Journal of Biological Chemistry

270

206

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Recently, microRNAs have emerged as regulators of cancer metastasis through acting on multiple signaling pathways involved in metastasis. In this study, we have analyzed the level of miR-10b and cell motility and invasiveness in several human esophageal squamous cell carcinoma cell lines. Our results reveal a significant correlation of miR-10b level with cell motility and invasiveness. Overexpression of miR-10b in KYSE140 cells increased cell motility and invasiveness, whereas inhibition of miR-10b in EC9706 cells reduced cell invasiveness, although it did not alter cell motility. Additionally, we identified KLF4, a known tumor suppressor gene that has been reported to suppress esophageal cancer cell migration and invasion, as a direct target of miR-10b. MicroRNAs, a class of small noncoding RNAs, have been identified as a new kind of gene expression regulators through targeting mRNAs for translational repression or cleavage (1-3). Lately, emerging evidence suggests important roles for miRNAs 2 in apoptosis (4), hematopoietic development (5), cell proliferation (6), skin morphogenesis (7), and neural development (8). Deregulation of miRNAs has also been reported in a variety of tumors, including breast cancer, leukemia, lung cancer, and colon cancer (9 -11), which indicated a significant correlation between miRNAs and human malignancy. miRNA expression profiling in esophageal cancers revealed a distinct miRNA signature (12, 13), and some miRNAs showed correlation with several clinicopathologic parameters (13). Furthermore, miR-21 is reported to regulate the proliferation and invasion in ESCC (14), and the miR-106b-25 polycistron is activated by genomic amplification and is potentially involved in esophageal neoplastic progression (15), providing evidence of a causal role for miRNAs in esophageal cancer development.Recent studies show that miRNAs may act as activators or inhibitors of tumor metastasis by acting on multiple signaling pathways involved in metastasis (16 -18). Ma et al. (16) found that miR-10b initiates invasion and metastasis in breast cancer. miR10b, induced by the prometastatic transcription factor TWIST1, proceeds to inhibit translation of mRNA of HOXD10, a transcription factor already known for its roles in cell motility (19), resulting in increased expression of a pro-metastatic gene, RHOC. This study has provided the first evidence for a role of miRNA in tumor metastasis. Subsequently several additional miRNAs have been reported to act on various steps of metastasis (17, 18).Krüppel-like factor 4 (KLF4), a zinc finger protein of the Krüp-pel-like factor family, plays a role in cell cycle regulation, differentiation, and rises in response to DNA damage, serum starvation, and contact inhibition (20, 21). In line with these studies, the loss of KLF4 expression has been reported in several human tumors, including colorectal, stomach, esophageal, and bladder cancers (22-25), which indicates its tumor suppressor role. However, KLF4 also exhibits oncogenic properties. Overexpression of KLF4 could b...

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“…32 Furthermore, homozygous loss of the miR-31-encoding genomic locus has been described in human urothelial carcinoma 33 and acute lymphoblastic lymphoma. 34 On the other hand, several studies showed that miR-31 is upregulated in colorectal cancer, hepatocellular cancer and most squamous cell carcinomas.…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

et al. 2012

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microRNAs (miRNAs) have key roles in human tumorigenesis, tumor progression and metastasis. miRNAs are aberrantly expressed in many human cancers and can function as tumor suppressors or oncogenes that target many cancer-related genes. This study seeks to identify novel miRNA-regulated molecular pathways in prostate cancer (PCa). The miRNA expression signature in clinical specimens of PCa showed that 56 miRNAs were significantly downregulated in PCa compared with nonPCa tissues. We focused on the top four downregulated miRNAs (miR-187, miR-205, miR-222 and miR-31) to investigate their functional significance in PCa cells. Expression levels of these four miRNAs were validated in PCa specimens (15 PCa tissues and 17 non-PCa tissues) to confirm that they were significantly reduced in these PCa tissues. Gain-of-function analysis demonstrated that miR-222 and miR-31 inhibited cell proliferation, invasion and migration in PCa cell lines (PC3 and DU145), suggesting that miR-222 and miR-31 may act as tumor suppressors in PCa. Genome-wide gene expression analysis using miR-222 or miR-31 transfectants to identify the pathways they affect showed that many cancer-related genes are regulated by these miRNAs in PC3 cells. Identification and categorization of the molecular pathways regulated by tumor suppressive miRNAs could provide new information about the molecular mechanisms of PCa tumorigenesis.

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MiRNA expression in urothelial carcinomas: Important roles of miR‐10a, miR‐222, miR‐125b, miR‐7 and miR‐452 for tumor stage and metastasis, and frequent homozygous losses of miR‐31

Cited by 206 publications

References 50 publications

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

Dysregulation of microRNA‐204 mediates migration and invasion of endometrial cancer by regulating FOXC1

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Tumor suppressive microRNAs (miR-222 and miR-31) regulate molecular pathways based on microRNA expression signature in prostate cancer

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