MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior

Roldo, Claudia; Missiaglia, Edoardo; Hagan, John P.; Falconi, Massimo; Capelli, Paola; Bersani, Samantha; Calin, George A.; Volinia, Stefano; Liu, Chang Gong; Scarpa, Aldo; Croce, Carlo M.

doi:10.1200/jco.2005.05.5194

Cited by 702 publications

(584 citation statements)

References 38 publications

Supporting

Mentioning

554

Contrasting

Unclassified

Order By: Relevance

“…miR-194 has been reported to be involved in the regulation of pancreatic cancer metastasis 18 and miR-204 in pancreatic acinar cell carcinoma transformation and progression. 19 Cell adhesion …”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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 ...

show abstract

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

show abstract

“…MicroRNAs (miRNAs) are a class of small non-coding RNAs approximately 21 nucleotides in length that regulate diverse cellular processes including decision of cell lineage, stem cell division, development in evolutionarily divergent organisms, tumorigenesis, and tumor cell metastasis [3,4]. These evidences suggest that miRNAs may be valuable therapeutic agents for their roles in modulating the differentiation of human tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR

Huang¹,

Chang²,

Chen³

et al. 2011

FEBS Letters

View full text Add to dashboard Cite

a b s t r a c tNeuroblastoma is the most common extracranial solid tumor in children. We investigate whether miR-124, the abundant neuronal miRNA, plays a pivotal role in neuroblastoma. Knockdown of miR-124 promotes neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis. Further miR-124 is predicted to target aryl hydrocarbon receptor (AHR) which may promote neuroblastoma cell differentiation. We validate that miR-124 may suppress the expression of AHR by targeting its 3 0 -UTR. These results suggest that miR-124 could serve as a potential therapeutic target of neuroblastoma.

show abstract

“…[8][9][10][11][12][13][14] Prognostic and diagnostic significance of miRNA expression has been reported in several malignancies, including chronic lymphocytic leukemia, breast, pancreas, colon and lung carcinomas. [15][16][17][18][19] Let-7 was the first miRNA reported to be aberrantly expressed in lung carcinomas. [20][21][22] It has been found that let-7 miRNA family controls the activity of RAS genes and function as tumor suppressor gene.…”

mentioning

confidence: 99%

miRNA expression profiling of lung adenocarcinomas: correlation with mutational status

et al. 2010

View full text Add to dashboard Cite

MicroRNA (miRNA) expression is deregulated in lung cancer, and some miRNAs are associated with poor prognosis and survival. In this study, we investigated the miRNA expression in lung adenocarcinomas with different oncogenic mutations, including EGFR-positive, KRAS-positive and EGFR/KRAS-negative tumors. The expression of 319 miRNAs was evaluated by Exiqon/Luminex microarray, and expression of individual miRNAs was validated by individual RT-PCR assays (Applied Biosystems). Overall, miRNA expression was similar among three mutationally different groups with most upregulated miRNAs being miR-20a, miR-328, miR-34c and miR-18b and most downregulated miRNAs being miR-32, miR-137 and miR-342. Four miRNAs (miR-155, miR-25, miR-495 and miR-7g) were expressed differently among these tumors. miR-155 was upregulated only in EGFR/KRAS-negative group, miR-25 was upregulated only in EGFR-positive group and miR-495 was upregulated only in KRAS-positive adenocarcinomas. In opposite, let-7g was downregulated in all three groups, with more significant downregulation in EGFR/KRASnegative adenocarcinomas. Principal component analysis (PCA) revealed significant correlation between miRNA expression patterns and somatic mutations. In this study, we demonstrated that despite the similarity in miRNA expression among lung adenocarcinomas with different somatic mutations, some miRNAs showed unique expression patterns, which were in strong correlation with the mutation type, suggesting different carcinogenic pathway for these tumors. These miRNAs can be further explored for their diagnostic and prognostic use.

show abstract

MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior

Abstract: These results suggest that alteration in microRNA expression is related to endocrine and acinar neoplastic transformation and progression of malignancy, and might prove useful in distinguishing tumors with different clinical behavior.

Cited by 702 publications

References 38 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

Silencing of miR-124 induces neuroblastoma SK-N-SH cell differentiation, cell cycle arrest and apoptosis through promoting AHR

miRNA expression profiling of lung adenocarcinomas: correlation with mutational status

Contact Info

Product

Resources

About