Downregulation of microRNAs-143 and -145 in B-cell malignancies.
Recently, it has been found that inappropriate expression of microRNAs (miRNAs) is strongly associated with carcinogenesis. In this study, we demonstrated that the expression of miRNAs (miRs) -143 and -145, the levels of which were previously shown to be reduced in colon cancers and various kinds of established cancer cell lines, was also decreased in most of the B-cell malignancies examined, including chronic lymphocytic leukemias (CLL), B-cell lymphomas, Epstein-Barr virus (EBV)-transformed B-cell lines, and Burkitt lymphoma cell lines. All samples from 13 CLL patients and eight of nine B-cell lymphoma ones tested exhibited an extremely low expression of miRs-143 and -145. The expression levels of miRs-143 and -145 were consistently low in human Burkitt lymphoma cell lines and were inversely associated with the cell proliferation observed in the EBV-transformed B-cell lines. Moreover, the introduction of either precursor or mature miR-143 and -145 into Raji cells resulted in a significant growth inhibition that occurred in a dose-dependent manner and the target gene of miRNA-143 was determined to be ERK5, as previously reported in human colon cancer DLD-1 cells. Taken together, these findings suggest that miRs-143 and -145 may be useful as biomarkers that differentiate B-cell malignant cells from normal cells and contribute to carcinogenesis in B-cell malignancies by a newly defined mechanism.
Akao
Yukihiro
Y
Department of Medical Oncology, Gifu International Institute of Biotechnology, 1-1 Naka-Fudogaoka, Kakamigahara, Gifu 504-0838, Japan. yakao@giib.or.jp
Nakagawa
Yoshihito
Y
Kitade
Yukio
Y
Kinoshita
Tomohiro
T
Naoe
Tomoki
T
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D000077209:Decitabine; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D012334:RNA, Neoplasm / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D006877:Hydroxamic Acids; D035683:MicroRNAs; D012334:RNA, Neoplasm; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine