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   ADAM12-L  and  ADAM12-S  represent two major splice variants of human metalloproteinase-disintegrin 12 mRNA, which differ in their 3′-untranslated regions (3′UTRs).  ADAM12-L , but not  ADAM12-S , has prognostic and chemopredictive values in breast cancer. Expression levels of the two  ADAM12  splice variants in clinical samples are highly discordant, suggesting post-transcriptional regulation of the  ADAM12  gene. The miR-29, miR-30, and miR-200 families have potential target sites in the  ADAM12-L  3′UTR and they may negatively regulate  ADAM12-L  expression.    Methods  miR-29b/c, miR-30b/d, miR-200b/c, or control miRNA mimics were transfected into SUM159PT, BT549, SUM1315MO2, or Hs578T breast cancer cells.  ADAM12-L  and  ADAM12-S  mRNA levels were measured by qRT-PCR, and ADAM12-L protein was detected by Western blotting. Direct targeting of the  ADAM12-L  3′UTR by miRNAs was tested using an  ADAM12-L  3′UTR luciferase reporter. The rate of  ADAM12-L  translation was evaluated by metabolic labeling of cells with  35 S cysteine/methionine. The roles of endogenous miR-29b and miR-200c were tested by transfecting cells with miRNA hairpin inhibitors.    Results  Transfection of miR-29b/c mimics strongly decreased  ADAM12-L  mRNA levels in SUM159PT and BT549 cells, whereas  ADAM12-S  levels were not changed.  ADAM12-L , but not  ADAM12-S , levels were also significantly diminished by miR-200b/c in SUM1315MO2 cells. In Hs578T cells, miR-200b/c mimics impeded translation of  ADAM12-L  mRNA. Importantly, both miR-29b/c and miR-200b/c strongly decreased steady state levels of ADAM12-L protein in all breast cancer cell lines tested. miR-29b/c and miR-200b/c also significantly decreased the activity of an  ADAM12-L  3′UTR reporter, and this effect was abolished when miR-29b/c and miR-200b/c target sequences were mutated. In contrast, miR-30b/d did not elicit consistent and significant effects on ADAM12-L expression. Analysis of a publicly available gene expression dataset for 100 breast tumors revealed a statistically significant negative correlation between  ADAM12-L  and both miR-29b and miR-200c. Inhibition of endogenous miR-29b and miR-200c in SUM149PT and SUM102PT cells led to increased  ADAM12-L  expression.    Conclusions  The  ADAM12-L  3′UTR is a direct target of miR-29 and miR-200 family members. Since the miR-29 and miR-200 families play important roles in breast cancer progression, these results may help explain the different prognostic and chemopredictive values of  ADAM12-L  and  ADAM12-S  in breast cancer.

ADAM12-L is a direct target of the miR-29 and miR-200 families in breast cancer