Dataset Information

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

ABSTRACT: A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0.0001). The ratio of cancer to benign miR-182 expression per patient was inversely associated with recurrence in a multivariate logistic regression model (odds ratio = 0.18; 95% CI, 0.03-0.89; P = 0.044). Correlation of miR-182 with mRNA expression in laser-capture microdissected benign prostate epithelium was used to predict prostatic miR-182 targets. Genes that were negatively correlated with miR-182 were enriched for its predicted targets and for genes previously identified as up-regulated in prostate cancer metastases. miR-182 expression was also negatively correlated with genes previously identified as up-regulated in primary prostate tumors from African American patients, who are at an increased risk of developing aggressive prostate cancer. Taken together, these results suggest that although miR-182 is expressed at higher levels in localized prostate cancer, its levels are lower in aggressive cancers, suggesting a biphasic role for this miRNA that may be exploited for prognostic and/or therapeutic purposes to reduce prostate cancer progression.

SUBMITTER: Baumann B

PROVIDER: S-EPMC6446228 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Association of High miR-182 Levels with Low-Risk Prostate Cancer.

Baumann Bethany B Acosta Andrés M AM Richards Zachary Z Deaton Ryan R Sapatynska Anastasiya A Murphy Adam A Kajdacsy-Balla Andre A Gann Peter H PH Nonn Larisa L

The American journal of pathology 20190129 4

A subset of men with prostate cancer develops aggressive disease. We sought to determine whether miR-182, an miRNA with reported oncogenic functions in the prostate, is associated with biochemical recurrence and aggressive disease. Prostate epithelial miR-182 expression was quantified via in situ hybridization of two prostate tissue microarrays and by laser-capture microdissection of prostate epithelium. miR-182 was significantly higher in cancer epithelium than adjacent benign epithelium (P < 0 ...[more]

PMID: 30703341

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Project description:The relationship between miR-21 and miR-182 gene expression in peripheral blood and gastric cancer tissue was investigated, exploring the relationship between the levels of miR-21 and miR-182 and prognosis of gastric cancer patients, and determining the effects of these two genes on the growth and migration of gastric cancer cells. Fifty gastric cancer patients who were treated in the 254th Hospital of PLA, from July 2012 to July 2014 were selected. Peripheral blood samples were drawn from patients, and 50 healthy subjects were studied as controls. The levels of the miR-21 and miR-182 genes were detected by semi-quantitative PCR, and the correlation between miR-21 and miR-182 expression and clinicopathological features was explored. Moreover, the effects of miR-21 and miR-182 expression on the survival time and prognosis of patients were investigated. siRNA was used to downregulate miR-21 and miR-182 gene expression in MGC-803 gastric cancer cells, and MTT and Transwell assays were conducted. As a result, the relative expression levels of miR-21 and miR-182 in peripheral blood of gastric cancer patients were significantly higher than in healthy subjects (p<0.01) and the relative expression of miR-182 was closely related to the clinicopathological features of gastric cancer patients (p<0.05); high expression of miR-21 and miR-182 was associated with reduced survival time of patients (p<0.05); MGC-803 cells with low expression of miR-21 and miR-182 were analyzed, showing that miR-182 promoted cell proliferation and migration (p<0.01). In conclusion, the relative levels of miR-21 and miR-182 in peripheral blood of patients with gastric cancer are significantly increased; low expression of miR-182 can significantly reduce the proliferation and migration of gastric cancer cells. Moreover, miR-182 expression, which is closely related to the clinicopathological features of gastric cancer, can serve as a target for the clinical treatment of gastric cancer.

Project description:ObjectiveTo validate six previously identified markers among men at increased risk of prostate cancer (African-American men and those with a family history of prostate cancer) enrolled in the Prostate Cancer Risk Assessment Program (PRAP), a prostate cancer screening study.Patients and methodsEligibility criteria for PRAP include age 35-69 years with a family history of prostate cancer, African-American ethnicity regardless of family history, and known BRCA gene mutations. The genome-wide association study markers assessed included rs2736098 (5p15.33), rs10993994 (10q11), rs10788160 (10q26), rs11067228 (12q24), rs4430796 (17q12) and rs17632542 (19q13.33). Genotyping methods included either the Taqman(®) single nucleotide polymorphism (SNP) genotyping assay (Applied Biosystems, Foster City, CA, USA) or pyrosequencing. Linear regression models were used to evaluate the association between individual markers and log-transformed baseline PSA levels, while adjusting for potential confounders.ResultsA total of 707 participants (37% Caucasian, 63% African-American) with clinical and genotype data were included in the analysis. Rs10788160 (10q26) was strongly associated with PSA levels among Caucasian participants in the high-risk group (P < 0.01), with a 33.2% increase in PSA level with each A-allele carried. Furthermore, rs10993994 (10q11) was found to be associated with PSA level (P = 0.03) in Caucasian men in the high-risk group, with a 15% increase in PSA level with each T-allele carried. A PSA adjustment model based on allele carrier status at rs10788160 and rs10993994 was proposed, specific to high-risk Caucasian men.ConclusionsGenetic variation at 10q may be particularly important in personalizing the interpretation of PSA level for Caucasian men in the high-risk group. Such information may have clinical relevance in shared decision-making and individualized prostate cancer screening strategies for Caucasian men in the high-risk group, although further study is warranted.

Dataset Information

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

Publications

Association of High miR-182 Levels with Low-Risk Prostate Cancer.

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