Unknown,Transcriptomics,Genomics,Proteomics

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MicroRNA profiling of follicular lymphoma cells

ABSTRACT: The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications. miRNA profiling was performed using Agilent miRNA array platform with RNAs isolated from sorted follicular lymphoma B cells and follicular hyperplasia B cells.

ORGANISM(S): Homo sapiens

SUBMITTER: Weixin Wang

PROVIDER: E-GEOD-28090 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response.

Wang Weixin W Corrigan-Cummins Meghan M Hudson Justin J Maric Irina I Simakova Olga O Neelapu Sattva S SS Kwak Larry W LW Janik John E JE Gause Barry B Jaffe Elaine S ES Calvo Katherine R KR

Haematologica 20111118 4

<h4>Background</h4>MicroRNAs can play an important role in tumorigenesis through post-transcriptional regulation of gene expression, and are not well characterized in follicular lymphoma.<h4>Design and methods</h4>MicroRNA profiles of enriched follicular lymphoma tumor cells from 16 patients were generated by assaying 851 human microRNAs. Tandem gene expression profiles were obtained for predicting microRNA targets.<h4>Results</h4>The expression of 133 microRNAs was significantly different (> 2- ...[more]

PMID: 22102710

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Project description:The hallmark of follicular lymphoma (FL) is the t(14;18) chromosomal translocation. However, constitutive expression of anti-apoptotic Bcl-2 alone is insufficient for lymphomagenesis and subsequent molecular hits are required. We explored the role of microRNA (miRNA or miR) in the biology of FL by generating miRNA profiles of enriched sorted grade 1 and 2 FL tumor cells derived from 18 patients compared with enriched germinal center B-cells derived from seven follicular hyperplasia (FH). Expression levels of 851 human miRs were assayed and 133 miRs were significantly differentially expressed in FL tumor cells. The expression of 44 miRs in three major groups generated a unique FL signature. MiRs in group 1 were increased in FL (miR-193-5p, -193b*, -345, -513b, -574-3p, -584, -663, -1287, -1295, and -1471). Group 2 was increased in the majority of FL cases but showed lower levels of expression in a subset of FL (let-7a, let-7f, miR-7-1*, -9, -9*, -20a, -20b, -30b, -96, -98, -194, -195, -221*, -374a, -451, -454, -502-3p, -532-3p, -574-3p, -664*, -1274a, -1274b, and -1260). MiR group 3 was decreased in FL (miR-17*, -30a, 33a, 106a*, -141, 202, -205, -222, 301b, -431*, and -570). Two patterns within FL were detected, largely due to the variable expression of group 2 miRs. The pattern with higher expression of group 2 miRs was associated with complete response to chemotherapy. Gene expression analysis of 199 genes related to lymphoma and tumor development performed in tandem indicated differential expression of 47 genes in FL including increased expression of AKT-1, PRKCE, IL4R, DROSHA, and MAPK1; and decreased expression of CHEK1, RAD51, CDKN1A, SOCS2, KLF4, BLIMP1 and IRF4. Functional studies provide evidence that miR-20a and -20b target CDKN1A/p21, miR-194 targets SOCS2, and miR-301b targets MAPK1 in FL, affecting cell proliferation and potentially contributing to lymphomagenesis. These findings suggest a role for aberrant miRNA expression in the biology of FL with prognostic and mechanistic implications.

Project description:Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Conclusion: Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy. Two miRNA arms from the same precursor, miR-574-5p and miR-574-3p, were reversely expressed and played exact opposite role in gastric cancer progression. miR-574-5p/-3p ratio was also strongly correlated with higher TNM stages and shorter survival of patients. The increase of miR-574-5p/-3p ratio, or the arm-imbalance of miR-574 was due to the dynamic expression of their highly complementary targets in gastric carcinogenesis. The arm imbalance of miR-574 in turn strongly contributed to and further promoted gastric cancer progression. Our findings indicated that targets mediated miR-574 arm-imbalance contributed to gastric cancer progression. Re-modification of the miR-574-targets homeostasis may represent a realistic approach for gastric cancer prevention and therapy.

Dataset Information

MicroRNA profiling of follicular lymphoma cells

Publications

MicroRNA profiling of follicular lymphoma identifies microRNAs related to cell proliferation and tumor response.

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