English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background  The  miR-9  family microRNAs have been identified as a tumor suppressor miRNA in cancers. We postulated that  miR-9-1 ,  miR-9-2  and  miR-9-3  might be inactivated by DNA hypermethylation in chronic lymphocytic leukemia (CLL).    Methods  Methylation of  miR-9-1 ,  miR-9-2  and  miR-9-3  was studied in eight normal controls including normal bone marrow, buffy coat, and CD19-sorted peripheral blood B-cells from healthy individuals, seven CLL cell lines, and seventy-eight diagnostic CLL samples by methylation-specific polymerase chain reaction.    Results  The promoters of  miR-9-3  and  miR-9-1  were both unmethylated in normal controls, but methylated in five (71.4%) and one of seven CLL cell lines respectively. However,  miR-9-2  promoter was methylated in normal controls including CD19 + ve B-cells, hence suggestive of a tissue-specific but not tumor-specific methylation, and thus not further studied. Different MSP statuses of  miR-9-3 , including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite methylation analysis. 5-Aza-2′-deoxycytidine treatment resulted in  miR-9-3  promoter demethylation and re-expression of  pri-miR-9-3  in I83-E95 and WAC3CD5+ cells, which were homozygously methylated for  miR-9-3 . Moreover, overexpression of  miR-9  led to suppressed cell proliferation and enhanced apoptosis together with downregulation of NFκB1 in I83-E95 cells, supporting a tumor suppressor role of  miR-9-3  in CLL. In primary CLL samples,  miR-9-3  was detected in 17% and  miR-9-1  methylation in none of the patients at diagnosis. Moreover,  miR-9-3  methylation was associated with advanced Rai stage (≥ stage 2) (P = 0.04).    Conclusions  Of the  miR-9  family,  miR-9-3  is a tumor suppressor miRNA relatively frequently methylated, and hence silenced in CLL; whereas  miR-9-1  methylation is rare in CLL. The role of  miR-9-3  methylation in the constitutive activation of NFκB signaling pathway in CLL warrants further study.

Epigenetic inactivation of miR-9 family microRNAs in chronic lymphocytic leukemia - implications on constitutive activation of NFκB pathway