microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma.
Mantle cell lymphoma (MCL) is one of the most aggressive B-cell lymphomas. Although several protein-coding genes are altered, expression signature and importance of microRNA (miRNA) have not been well documented in this malignancy. Here, we performed miRNA expression profile in 30 patients with MCL using a platform containing 515 human miRNAs. Eighteen miRNAs were down-regulated and 21 were up-regulated in MCL compared with normal B lymphocytes. The most frequently altered miRNAs are decrease of miR-29a/b/c, miR-142-3p/5p, and miR-150 and increase of miR-124a and miR-155. Notably, expression levels of miR-29 family are associated with prognosis. The patients with significant down-regulated miR-29 had short survival compared with those who express relatively high levels of miR-29. The prognostic value of miR-29 is comparable with the Mantle Cell Lymphoma International Prognostic Index. Furthermore, we demonstrate miR-29 inhibition of CDK6 protein and mRNA levels by direct binding to 3'-untranslated region. Inverse correlation between miR-29 and CDK6 was observed in MCL. Because cyclin D1 overexpression is a primary event and exerts its function through activation of CDK4/CDK6, our results in primary MCL cells indicate that down-regulation of miR-29 could cooperate with cyclin D1 in MCL pathogenesis. Thus, our findings provide not only miRNA expression signature but also a novel prognostic marker and pathogenetic factor for this malignancy.
Zhao
Jian-Jun
JJ
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
Lin
Jianhong
J
Lwin
Tint
T
Yang
Hua
H
Guo
Jianping
J
Kong
William
W
Dessureault
Sophie
S
Moscinski
Lynn C
LC
Rezania
Dorna
D
Dalton
William S
WS
Sotomayor
Eduardo
E
Tao
Jianguo
J
Cheng
Jin Q
JQ
D020413:3' Untranslated Regions / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000378:metabolism; D014408:Biomarkers, Tumor; D019938:Cyclin D1 / Q000502:physiology; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D020413:3' Untranslated Regions; D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D019938:Cyclin D1; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6