Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels

Muralidhar, Balaji; Goldstein, Leonard D.; Ng, Grace; Winder, DM; Palmer, Roger D.; Gooding, Emma L.; Barbosa‐Morais, Nuno L.; Mukherjee, Geetashree; Thorne, Natalie; Roberts, Ian; Pett, Mark R.; Coleman, Nicholas

doi:10.1002/path.2179

Cited by 156 publications

(142 citation statements)

References 36 publications

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“…Expression levels of four most significantly upregulated miRNAs and four most significantly down-modulated miRNAs in NPC tissues were shown in Figure 2A and B. The global alteration in miRNA expression pattern observed in our study is similar to earlier reports on other human cancers (Lu et al, 2005;Muralidhar et al, 2007).…”

Section: Identification Of Differentially Expressed Mirna In Human Npcsupporting

confidence: 90%

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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Section: Identification Of Differentially Expressed Mirna In Human Npcsupporting

confidence: 90%

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

et al. 2009

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“…This would be in keeping with multiple other studies showing dysregulation of parts of the pathway in cancer cell lines and tissues. 37,38 It is likely that there is a complex interaction between microRNA processing machinery, already abnormal in cancer cells, 39 and microRNA induced in hypoxia. It may also reflect post-translational processes such as prolyl 4-hydroxylation: the same process that regulates von Hippel-Lindau gene, and in turn HIFm, regulates Argonaute 2 stability.…”

Section: Discussionmentioning

confidence: 99%

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

Gee

Camps

Buffa

et al. 2010

Cancer

201

157

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BACKGROUND:Hypoxia is an important mechanism of treatment resistance in head and neck squamous cell carcinoma (HNSCC). MicroRNAs are short noncoding RNAs that regulate multiple mRNAs and are frequently dysregulated in cancer. The authors have investigated the role of 3 microRNAs, including the hypoxia-induced hsa-miR-210, as potential markers of hypoxia or prognosis. METHODS: Three hypoxia-related microRNAs, hsa-miR-210, hsa-miR-21, and hsa-miR-10b, were measured in 46 samples from patients with HNSCC. Expression levels were correlated with clinicopathological variables and other markers of hypoxia: a published 99-gene hypoxia metagene, individual hypoxia-related genes such as TWIST1, and immunohistochemical expression of hypoxia-inducible factor 1 and its target gene carbonic anhydrase 9. We then performed survival analyses to investigate the prognostic significance of these microRNAs. RESULTS: Only the level of hsa-miR-210 was significantly correlated with other markers of hypoxia, including the 99-gene hypoxia metagene (rho ¼ 0.67, P < .001). We found no association between hsa-miR-210, hsamiR-21, or hsa-miR-10b and clinicopathological variables such as tumor size, differentiation, and stage. However, high levels of hsa-miR-210 were associated with locoregional disease recurrence (P ¼ .001) and short overall survival (P ¼ .008). hsa-miR-21 and hsa-miR-10b had no prognostic significance. CONCLUSIONS: Expression of hsa-miR-210 in head and neck cancer correlates with other approaches for assessing hypoxia and is associated with prognosis. This warrants further study as a classification marker of patients for therapies involving modulation of hypoxia.

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“…55,56 In addition, global microRNA profiling has showed that Drosha overexpression in cervical squamous cell carcinoma appears to be of functional significance. 57 However, despite evidence for decreased Dicer levels leading to a decrease in microRNA let -7, 7 no definitive evidence linking global alterations in microRNA profiles to Dicer levels has been demonstrated to date. In fact, increased Dicer expression was observed in lung adenocarcinoma relative to normal alveolar epithelium in a tumour where global downregulation of microRNA has been reported.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2008

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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. Production and function of microRNAs require coordinated processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III endonucleases) are essential components of the microRNA machinery. Recently, the ribosome anti-association factor eIF6 has also been found to have a role in microRNA-mediated post-transcriptional silencing. We characterized the alterations in the expression of genes encoding proteins of microRNA machinery in ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA expression was analysed using quantitative reverse transcription-PCR on an independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma samples. Expression profiles of eIF6 and Dicer were correlated with clinicopathological and patient survival data. We provide definitive evidence that eIF6 and Dicer are both upregulated in a significant proportion of ovarian serous carcinomas and are associated with specific clinicopathological features, most notably low eIF6 expression being associated with reduced disease-free survival. The status of eIF6 and proteins of the microRNA machinery may help predict toxicity and susceptibility to future interfering RNA-based therapy.

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Global microRNA profiles in cervical squamous cell carcinoma depend on Drosha expression levels

Cited by 156 publications

References 36 publications

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

MicroRNA deregulation and pathway alterations in nasopharyngeal carcinoma

hsa‐miR‐210 is a marker of tumor hypoxia and a prognostic factor in head and neck cancer

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

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