Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

Flavin, Richard; Smyth, Paul; Finn, Stephen P.; Laios, Alexandros; O’Toole, Sharon; Barrett, Ciara; Ring, Martina; Denning, K; Li, Jinghuan; Aherne, Sinéad; Aziz, Natasha; Alhadi, Araibi; Sheppard, B. L.; Loda, Massimo; Martin, Cara; Sheils, Orla; O’Leary, John

doi:10.1038/modpathol.2008.33

Cited by 94 publications

(110 citation statements)

References 52 publications

(45 reference statements)

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“…Recently, dysregulation of Dicer in malignancies has been of great interest in oncology. Studies have shown that Dicer is upregulated in prostate adenocarcinomas, ovarian serous carcinomas, esophageal cancers and acute myeloid leukemia (AML), and downregulated in hepatocellular carcinomas, lung cancers and ovarian carcinomas (17)(18)(19). The present study showed that Dicer was downregulated in TCCs compared to their NAT samples or normal bladder mucosae.…”

Section: Discussionsupporting

confidence: 54%

Downregulation of Dicer, a component of the microRNA machinery, in bladder cancer

Wu¹,

Tao

et al. 2011

Mol Med Report

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Abstract. Dysregulation of microRNA metabolism has been observed in a variety of human cancers. In this study, we evaluated the expression of the enzymes of the machinery Dicer, Drosha and DGCR8, in transitional cell carcinomas (TCCs) of the urinary bladder. The expression of Dicer, Drosha and DGCR8 was analyzed using semi-quantitative RT-PCR in clinical specimens from normal bladder mucosa, TCCs and their normal adjacent tissues (NATs). Immunohistochemistry was performed to compare the expression of Dicer in normal, TCCs and NATs. Our study demonstrated that Dicer mRNA levels in TCCs were significantly lower compared to normal samples and NAT samples. The immunohistochemistry results revealed that Dicer protein levels in TCCs were significantly downregulated compared to normal bladder mucosa and NATs. Our data demonstrated that Dicer is significantly downregulated in TCCs compared to paired NAT samples and normal samples, suggesting that reduced expression of Dicer may play an important role in bladder cancer.

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Section: Discussionsupporting

confidence: 54%

Downregulation of Dicer, a component of the microRNA machinery, in bladder cancer

Wu¹,

Tao

et al. 2011

Mol Med Report

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“…19 Furthermore, our group has demonstrated dysregulation of Dicer and Drosha proteins (both of which coordinate micro-RNA processing) in ovarian serous carcinoma. 64 Recent research suggests that DNA methylation may also be involved in the regulation of microRNA expression in ovarian cancer, and the methylation can be reversed by DNA methyltransferase inhibitors. 9,65 Indeed, microRNA control and deregulation may be more complex as widespread microRNA repression by transcription factors such as c-myc (that targets miR-195/miR-497) have also been found to contribute to tumourigenesis.…”

Section: Discussionmentioning

confidence: 99%

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

et al. 2009

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MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in length. Recent work has shown differential expression of mature microRNAs in human cancers. We characterized the alteration in expression of a select group of microRNAs in primary peritoneal carcinoma relative to matched cases of ovarian serous carcinoma. MicroRNA expression was analysed using semi-quantitative stem-loop RT-PCR on a set of 34 formalin-fixed paraffin-embedded samples. Protein expression of p53 and bcl-2 was quantified in the corresponding tissue microarray. We provide definitive evidence that there is downregulation of a select group of microRNAs in tumours meeting Gynaecological Oncology Group criteria for primary peritoneal carcinoma relative to ovarian serous carcinoma. Specifically, we show decreased p53 expression and downregulation of miR-195 and miR-497 from the microRNA cluster site at chromosome 17p13.1 in primary peritoneal carcinoma relative to ovarian serous carcinoma. miR-195 and miR-497 may have potential roles as tumour-suppressor genes in primary peritoneal tumourigenesis.

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“…Forced expression of miR-143 and miR-145 inhibit cell growth in cervical cancer cells (Wang et al, 2008). Although the biological function of miR-195 and miR-497 has not been characterised, reduced expression of miR-195 and miR-497 on the 17p13 locus has been documented in primary peritoneal carcinoma (Flavin et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

et al. 2009

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MicroRNAs (miRNAs) are a family of small non-coding RNA molecules of about 20 -23 nucleotides in length, which negatively regulate protein-coding genes at post-transcriptional level. Using a stem-loop real-time-PCR method, we quantified the expression levels of 270 human miRNAs in 13 nasopharyngeal carcinoma (NPC) samples and 9 adjacent normal tissues, and identified 35 miRNAs whose expression levels were significantly altered in NPC samples. Several known oncogenic miRNAs, including miR-17-92 cluster and miR-155, are among the miRNAs upregulated in NPC. Tumour suppressive miRNAs, including miR-34 family, miR-143, and miR-145, are significantly downregulated in NPC. To explore the roles of these dysregulated miRNAs in the pathogenesis of NPC, a computational analysis was performed to predict the pathways collectively targeted by the 22 significantly downregulated miRNAs. Several biological pathways that are well characterised in cancer are significantly targeted by the downregulated miRNAs. These pathways include TGF-Wnt pathways, G1-S cell cycle progression, VEGF signalling pathway, apoptosis and survival pathways, and IP3 signalling pathways. Expression levels of several predicted target genes in G1-S progression and VEGF signalling pathways were elevated in NPC tissues and showed inverse correlation with the down-modulated miRNAs. These results indicate that these downregulated miRNAs coordinately regulate several oncogenic pathways in NPC.

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Altered eIF6 and Dicer expression is associated with clinicopathological features in ovarian serous carcinoma patients

Cited by 94 publications

References 52 publications

Downregulation of Dicer, a component of the microRNA machinery, in bladder cancer

Downregulation of Dicer, a component of the microRNA machinery, in bladder cancer

Potentially important microRNA cluster on chromosome 17p13.1 in primary peritoneal carcinoma

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

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