Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma

McMillen, Brian D.; Aponte, Margarita; Liu, Zhaojian; Helenowski, Irene; Scholtens, Denise M.; Buttin, Barbara M.; Wei, Jian Jun

doi:10.1038/modpathol.2012.118

Cited by 40 publications

(30 citation statements)

References 31 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the case of miR-182, which has been described to be upregulated in breast carcinoma, to target specifically BRCA1 gene and to be involved in the resistance to PARP-1 inhibitors [41], [42], we identified a relationship between miR-182 expression and clinical outcome. Interestingly, an association between miR-21 and miR-182 expression to young patients with triple negative breast cancer, was proved in this work.…”

Section: Discussionmentioning

confidence: 96%

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

et al. 2014

View full text Add to dashboard Cite

IntroductionMicroRNAs are small, non coding regulatory molecules containing approximately 21 to 25 nucleotides. They function as controllers of expression at post transcriptional levels of most human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study is to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17, miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible interaction in triple-negative and non triple-negative primary breast cancers based on clinical outcome.Methods60 triple-negative and non triple-negative breast cancer cases, along with their corresponding normal samples were investigated in relation to the expression of the seven studied miRNAs using qPCR Syber Green.ResultsWe observed that miR-21, miR-146a and miR-182 were significantly over expressed in triple negative breast cancer. Moreover, miR-10b, miR-21 and miR-182 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma while only miR-10b was associated with grade III in non triple negative breast cancer cases. Almost all the analyzed microRNAs were strongly associated with patients’ genico-obstetric history in non triple negative breast cancer cases except for miR-34a. All the studied microRNAs were strongly correlated with the use of the contraceptive pills in non triple negative breast cancer groups. The additive effect of hormonal factors in triple negative breast cancer cases showed an association with all the studied miRs except for miR-34 and miR-146a.ConclusionThe studied microRNAs are strongly influenced by environmental factors especially with hormonal patients’ history. Moreover, miR-10b, miR-21 and miR-182 could be defined as biomarkers in breast cancer to predict both lymph node metastases and grade III occurrence.

show abstract

Section: Discussionmentioning

confidence: 96%

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

et al. 2014

View full text Add to dashboard Cite

show abstract

“…FOXO3 is known to regulate LKB1 gene transcription, and the LKB1 protein plays a key role in cell planar polarity during cell division [43]. FOXO3 downregulation has also recently been reported in high-grade serous ovarian carcinoma [44]. …”

Section: Discussionmentioning

confidence: 99%

Polarity gene alterations in pure invasive micropapillary carcinomas of the breast

et al. 2014

View full text Add to dashboard Cite

IntroductionPure invasive micropapillary carcinoma (IMPC) is a special type of breast carcinoma characterised by clusters of cells presenting polarity abnormalities. The biological alterations underlying this pattern remain unknown.MethodsPangenomic analysis (n = 39), TP53 (n = 43) and PIK3CA (n = 41) sequencing in a series of IMPCs were performed. A subset of cases was also analysed with whole-exome sequencing (n = 4) and RNA sequencing (n = 6). Copy number variation profiles were compared with those of oestrogen receptors and grade-matched invasive ductal carcinomas (IDCs) of no special type.ResultsUnsupervised analysis of genomic data distinguished two IMPC subsets: one (Sawtooth/8/16) exhibited a significant increase in 16p gains (71%), and the other (Firestorm/Amplifier) was characterised by a high frequency of 8q (35%), 17q (20% to 46%) and 20q (23% to 30%) amplifications and 17p loss (74%). TP53 mutations (10%) were more frequently identified in the amplifier subset, and PIK3CA mutations (4%) were detected in both subsets. Compared to IDC, IMPC exhibited specific loss of the 6q16-q22 region (45%), which is associated with downregulation of FOXO3 and SEC63 gene expression. SEC63 and FOXO3 missense mutations were identified in one case each (2%). Whole-exome sequencing combined with RNA sequencing of IMPC allowed us to identify somatic mutations in genes involved in polarity, DNAH9 and FMN2 (8% and 2%, respectively) or ciliogenesis, BBS12 and BBS9 (2% each) or genes coding for endoplasmic reticulum protein, HSP90B1 and SPTLC3 (2% each) and cytoskeleton, UBR4 and PTPN21 (2% each), regardless of the genomic subset. The intracellular biological function of the mutated genes identified by gene ontology analysis suggests a driving role in the clinicopathological characteristics of IMPC.ConclusionIn our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.

show abstract

“…The tumor dissemination of HGSOC originates in the contralateral ovary, followed by widespread metastasis within the abdominal cavity, peritoneal organs, and regional lymph nodes (1). Emerging data shows that some of the miRNA dysregulation may contribute to the aggressive metastasis of HGSOC, including miR-182 (2, 3) and miR-200 (4, 5) dysregulation. Currently, the targeted miRNA therapy for ovarian cancer invasion and metastasis has yet to be reported.…”

Section: Introductionmentioning

confidence: 99%

Anti-miR182 Reduces Ovarian Cancer Burden, Invasion, and Metastasis: An In Vivo Study in Orthotopic Xenografts of Nude Mice

Ayub²,

Liu

et al. 2014

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

High-grade serous ovarian carcinoma (HGSOC) is a fatal disease, and its grave outcome is largely due to widespread metastasis at the time of diagnosis. Current chemotherapies reduce tumor burden, but they do not provide long term benefits for cancer patients. The aggressive tumor growth and metastatic behavior characteristic of these tumors demand novel treatment options such as anti-microRNA treatment which is emerging as a potential modality for cancer therapy. MicroRNA-182 miR-182 overexpression contributes to aggressive ovarian cancer, largely by its negative regulation of multiple tumor suppressor genes involved in tumor growth, invasion, metastasis, and DNA instability. In this study, we examined the therapeutic potential of anti-miR-182 utilizing the animal orthotopic model to mimic human ovarian cancer using ovarian cancer cells SKOV3 (intrabursal xenografts) and OVCAR3 (IP injection). These models provide a valuable model system for the investigation of ovarian cancer therapy in vivo. Through a combination of imaging, histological, and molecular analyses, we found that anti-miR-182 treatment can significantly reduce tumor burden (size), local invasion, and distant metastasis compared to its control in both models. The bases of anti-miR-182 treatment are mainly through the restoration of miR-182 target expression, including but not limited to BRCA1, FOXO3a, HMGA2 and MTSS1. Overall, our results strongly suggest that anti-miR-182 can potentially be used as a therapeutic modality in treating HGSOC.

show abstract

Expression analysis of MIR182 and its associated target genes in advanced ovarian carcinoma

Cited by 40 publications

References 31 publications

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

Polarity gene alterations in pure invasive micropapillary carcinomas of the breast

Anti-miR182 Reduces Ovarian Cancer Burden, Invasion, and Metastasis: An In Vivo Study in Orthotopic Xenografts of Nude Mice

Contact Info

Product

Resources

About