Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

White, Nicole M.; Chow, T-F F; Mejia-Guerrero, Salvador; Diamandis, Maria; Rofael, Y.; Faragalla, Hala; Mankaruous, M.; Gabril, Manal; Girgis, Andrew H.; Yousef, George M.

doi:10.1038/sj.bjc.6605634

Cited by 89 publications

(88 citation statements)

References 77 publications

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“…miR-224 is reported to be overexpressed in various types of cancer (15)(16)(17)(18)(19)(20), and it plays critical roles in malignant phenotypes. Consistent with these previous observations, miR-224 was found to be upregulated in HepG2 cells in our study.…”

Section: Discussionmentioning

confidence: 99%

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miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Ma¹,

Tao²,

Gao³

et al. 2012

Oncology Letters

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Abstract. microRNAs (miRNAs) are a class of small non-coding RNAs that post-transcriptionally regulate gene expression. Increasing evidence has shown that the deregulation of miRNAs is linked to cancer. The overexpression of miR-224 has been reported in several human cancers. The aim of the present study was to investigate the function of miR-224 in the pathogenetic process of hepatocellular carcinoma (HCC), and the precise mechanism underlying its function. Both gain-of-function and loss-of function assays were conducted through transfection with miR-224 mimics and miR-224 inhibitors in the HepG2 liver carcinoma cell line. The data revealed that miR-224 exerts a significant role in promoting cell proliferation, migration and invasion. Western blot analysis showed that the phosphorylation levels of AKT positively correlated with endogenous levels of miR-224. In addition, results from a dual luciferase reporter assay showed that the expression of the serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A β isoform (PPP2R1B) is inhibited by miR-224; thus, it appears that PPP2R1B is a candidate target of miR-224 in HCC. These data suggest that miR-224 plays a significant role in HCC, possibly through the activation of the AKT signaling pathway by targeting PPP2R1B.

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Section: Discussionmentioning

confidence: 99%

“…The abnormal expression of miR-224 has been reported in several human cancers (15)(16)(17)(18)(19). Wang et al found that miR-224 is upregulated in HCC patients and HCC cell lines (20), and promotes HCC cell apoptosis by targeting the transcript expression levels of apoptosis inhibitor 5 (API-5).…”

Section: Introductionmentioning

confidence: 99%

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Ma¹,

Tao²,

Gao³

et al. 2012

Oncology Letters

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“…Interestingly, miR-142 was identified as the strongest signature associated with lymphocyte-specific gene expression and methylation across multiple cancer types in another study (9). Several recent cancer studies also supported the inhibitory effect on cell proliferation by miR-142-3p in pancreatic cancer (10) and miR-224 in ovarian cancer (11). The only miRNA that showed high expression in proliferative subtype and low expression in immunoreactive subtype is miR-218.…”

Section: Resultsmentioning

confidence: 72%

Learning regulatory programs by threshold SVD regression

Ma¹,

Xiao

Wong

2014

Proc. Natl. Acad. Sci. U.S.A.

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We formulate a statistical model for the regulation of global gene expression by multiple regulatory programs and propose a thresholding singular value decomposition (T-SVD) regression method for learning such a model from data. Extensive simulations demonstrate that this method offers improved computational speed and higher sensitivity and specificity over competing approaches. The method is used to analyze microRNA (miRNA) and long noncoding RNA (lncRNA) data from The Cancer Genome Atlas (TCGA) consortium. The analysis yields previously unidentified insights into the combinatorial regulation of gene expression by noncoding RNAs, as well as findings that are supported by evidence from the literature.regulatory program | SVD | sparse | multivariate | regression T he development of microarray and next-generation sequencing technologies has enabled rapid quantification of various genome-wide features (DNA sequences, gene expressions, noncoding RNA expressions, methylation, etc.) in a population of samples (1, 2). Large consortia have compiled genetic and molecular profiling data in an enormous number of tumors across hundreds of samples (3,4). A common challenge arising from these large-scale genomic studies is the inference of regulatory relationships between different genome-wide measurements from the complex biological systems where the number of predictors and responses often far exceeds the sample size.To formulate a statistical model for such regulatory relations, consider the situation depicted in Fig. 1 (see Fig. S1 for more detailed illustration of the model schema), where p regulators x = ðx 1 ; . . . ; x p Þ regulate q responses y = ðy 1 ; . . . ; y q Þ through r regulatory programs that are represented by hidden nodes, e.g., h 1 ; . . . ; h r . The activity h j of the jth program depends on the regulators connected to hidden node j, and h j in turn affects the level of the responses that are connected to node j. To express this model mathematically, we denote by u j and v j the unit vectors corresponding respectively to the input weights fa ij , i = 1; . . . ; pg and the output weights fb jk , k = 1; . . . ; qg of the jth program. Then the regulatory relations are represented as h j = σðxu j Þ and y = P r j=1 d j h j v′ j , where x, y are regarded as row vectors, u, v are regarded as column vectors, and σ() is a sigmoidal function. The aforementioned is a standard single-layer neural network model that is widely used in predictive modeling but could be impossible to learn in biological studies where sample size n is much smaller than p or q. Thus, we first simplify the model by taking σ to be the identity function. Then our model becomes h j = xu j , y = P r j=1 d j h j v′ j . We make the biologically plausible assumption that only a small subset of regulators is contributing to any program and that each program regulates only a small subset of responses. Under this assumption, u j and v j are sparse vectors in R p and R q , respectively. The magnitude of the output weight vector (denoted by d j ) repr...

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“…These results strongly suggested that miR-224 functioned as a tumour suppressor in PCa cells. Downregulation of miR-224 has also been reported in other types of human cancers, including ovarian, lung, and breast cancers, in addition to PCa [17][18][19][20][21]. Additionally, one study has shown that more aggressive PCa is associated with lower expression of miR-224 and that downregulation of miR-224 is associated with biochemical relapse [22].…”

Section: Discussionmentioning

confidence: 98%

“…Improved understanding of ncRNAs is necessary for continued progress in cancer research. MicroRNAs (miRNAs) are endogenous small ncRNA molecules (19)(20)(21)(22) bases in length) that regulate the expression of protein-coding genes by repressing translation or cleaving RNA transcripts in a sequencespecific manner [5]. A significant amount of evidence suggests that miRNAs are aberrantly expressed in many human cancers and play significant roles in the initiation, development, and metastasis of those cancers [6].…”

Section: Introductionmentioning

confidence: 99%

Tumour‐suppressive microRNA‐224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer

et al. 2014

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Edited by Tamas DalmayKeywords: miR-224 TPD52 Prostate cancer microRNA Tumour suppressor a b s t r a c t Our recent study of the microRNA expression signature of prostate cancer (PCa) revealed that microRNA-224 (miR-224) is significantly downregulated in PCa tissues. Here, we found that restoration of miR-224 significantly inhibits PCa cell migration and invasion. Additionally, we found that oncogenic TPD52 is a direct target of miR-224 regulation. Silencing of the TPD52 gene significantly inhibits cancer cell migration and invasion. Moreover, TPD52 expression is upregulated in cancer tissues and negatively correlates with miR-224 expression. We conclude that loss of tumour-suppressive miR-224 enhances cancer cell migration and invasion in PCa through direct regulation of oncogenic TPD52.

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Three dysregulated miRNAs control kallikrein 10 expression and cell proliferation in ovarian cancer

Cited by 89 publications

References 77 publications

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

miR-224 functions as an onco-miRNA in hepatocellular carcinoma cells by activating AKT signaling

Learning regulatory programs by threshold SVD regression

Tumour‐suppressive microRNA‐224 inhibits cancer cell migration and invasion via targeting oncogenic TPD52 in prostate cancer

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