Additional file 1: Figure S1 Flowchart of Pathway Analysis. Sequences of AMO-miR-21 oligonucleotides and seed sequences in miR-21.

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Heat maps illustrating unsupervised clustering of mRNAs that were differentially expressed between the treated group (T-calibrated) and the normal group (N-calibrated). BB down-regulation of STAT3 mRNA level in MM cells. MiR-21 directly targets the PDCD4 3′UTR. Transfection efficiency and localization of AMO-mir-21 in RPMI-8266 cells. BB and AMO-miR-21 induction of apoptosis.

BB and AMO-miR-21 induction of G2-phase cell cycle arrest. KEGG analysis of p53 signaling pathways. Proposed pathway of BB inhibition of miRNA-21 in MM cells. Background Berberine is a natural alkaloid derived from a traditional Chinese herbal medicine. It is known to modulate microRNA (miRNA) levels, although the mechanism for this action is unknown. Here, we previously demonstrate that the expression of 87 miRNAs is differentially affected by berberine in multiple myeloma cells. Among 49 miRNAs that are down-regulated, nine act as oncomirs, including miR-21.

Integrative analysis showed that 28 of the down-regulated miRNAs participate in tumor protein p53 (TP53) signaling and other cancer pathways. MiR-21 is involved in all these pathways, and is one of the most important oncomirs to be affected by berberine in multiple myeloma cells. Results We confirmed that berberine down-regulated miRNA-21 expression and significantly up-regulated the expression of programmed cell death 4 ( PDCD4), a predicted miR-21 target. Luciferase reporter assays confirmed that PDCD4 was directly regulated by miR-21. Bioinformatic analysis revealed that the miR-21 promoter can be targeted by signal transducer and activator of transcription 3 (STAT3).

Down-regulation of interleukin 6 (IL6) by berberine might lead to inhibition of miR-21 transcription through STAT3 down-regulation in multiple myeloma. Furthermore, both berberine and seed-targeting anti-miR-21 oligonucleotide induced apoptosis, G2-phase cell cycle arrest and colony inhibition in multiple myeloma cell lines. Depletion of PDCD4 by short interfering RNA could rescue berberine-induced cytotoxicity in multiple myeloma cells. Background Multiple myeloma (MM) is a clonal B cell malignancy characterized by proliferation of plasma cells (PCs) within the bone marrow (BM).

Globally, its incidence varies from 1 per 100,000 people in China to about 4 per 100,000 people in most developed countries [,]. MM is characterized by profound genomic instability involving both numerical and structural chromosomal aberrations of potential prognostic relevance [,]. Baca komik gratis serial cantik komik dewasa. Nearly half of MM tumors are hyperdiploid (HD) with multiple trisomies of non-random odd-numbered chromosomes, a low prevalence of chromosomal translocations involving the immunoglobulin heavy chain (IgH) locus at 14q32 and chromosome 13 deletion []. It has been suggested that chromosomal abnormalities and other types of genetic or epigenetic alterations might contribute to miRNA deregulation in cancer [-]. MiRNAs are a newly discovered class of endogenous non-coding small RNAs that regulate gene expression through degrading target mRNAs and/or suppressing their translation by binding to the 3′-untranslated region (3′-UTR) of target genes.