RGD Reference Report - MicroRNA MIR21 and T Cells in Colorectal Cancer. - Rat Genome Database

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MicroRNA MIR21 and T Cells in Colorectal Cancer.

Authors: Mima, K  Nishihara, R  Nowak, JA  Kim, SA  Song, M  Inamura, K  Sukawa, Y  Masuda, A  Yang, J  Dou, R  Nosho, K  Baba, H  Giovannucci, EL  Bowden, M  Loda, M  Giannakis, M  Bass, AJ  Dranoff, G  Freeman, GJ  Chan, AT  Fuchs, CS  Qian, ZR  Ogino, S 
Citation: Mima K, etal., Cancer Immunol Res. 2016 Jan;4(1):33-40. doi: 10.1158/2326-6066.CIR-15-0084. Epub 2015 Sep 29.
RGD ID: 11538337
Pubmed: PMID:26419959   (View Abstract at PubMed)
PMCID: PMC4703429   (View Article at PubMed Central)
DOI: DOI:10.1158/2326-6066.CIR-15-0084   (Journal Full-text)

The complex interactions between colorectal neoplasia and immune cells in the tumor microenvironment remain to be elucidated. Experimental evidence suggests that microRNA MIR21 (miR-21) suppresses antitumor T-cell-mediated immunity. Thus, we hypothesized that tumor MIR21 expression might be inversely associated with T-cell density in colorectal carcinoma tissue. Using 538 rectal and colon cancer cases from the Nurses' Health Study and the Health Professionals Follow-up Study, we measured tumor MIR21 expression by a quantitative reverse-transcription PCR assay. Densities of CD3(+), CD8(+), CD45RO (PTPRC)(+), and FOXP3(+) cells in tumor tissue were determined by tissue microarray immunohistochemistry and computer-assisted image analysis. Ordinal logistic regression analysis was conducted to assess the association of MIR21 expression (ordinal quartiles as a predictor variable) with T-cell density (ordinal quartiles as an outcome variable), adjusting for tumor molecular features, including microsatellite instability; CpG island methylator phenotype; KRAS, BRAF, and PIK3CA mutations; and LINE-1 methylation. We adjusted the two-sided alpha level to 0.012 for multiple hypothesis testing. Tumor MIR21 expression was inversely associated with densities of CD3(+) and CD45RO(+) cells (Ptrend < 0.0005). The multivariate odds ratio of the highest versus lowest quartile of MIR21 for a unit increase in quartile categories of CD3(+) or CD45RO(+) cells was 0.44 [95% confidence interval (CI), 0.28 to 0.68] or 0.41 (95% CI, 0.26-0.64), respectively. Our data support a possible role of tumor epigenetic deregulation by noncoding RNA in suppressing the antitumor T-cell-mediated adaptive immune response and suggest MIR21 as a potential target for immunotherapy and prevention in colorectal cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
colorectal cancer severityIEP 11538337RNA:increased expression:colorectum (human)RGD 
colorectal cancer severityISOMIR21 (Homo sapiens)11538337; 11538337RNA:increased expression:colorectum (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Mir21  (microRNA 21)

Genes (Mus musculus)
Mir21a  (microRNA 21a)

Genes (Homo sapiens)
MIR21  (microRNA 21)


Additional Information