An article published this year in “CELL DEATH AND DISEASE” using our IntraCell
Kit, by our customers from Laboratory of Preclinical and Translational
Research, IRCCS – Referral Cancer Center of Basilicata (CROB), Rionero in
Vulture, Italy, in the analysis of how Knockdown of miR-128a induces Lin28a
expression and reverts myeloid differentiation blockage in acute myeloid
leukemia. Congrats and Thanks.
Summary:
Lin28A is a highly conserved
RNA-binding protein that concurs to control the balance between stemness and
differentiation in several tissue lineages. Here, we report the role of
miR-128a/Lin28A axis in blocking cell differentiation in acute myeloid leukemia
(AML), a genetically heterogeneous disease characterized by abnormally
controlled proliferation of myeloid progenitor cells accompanied by partial or
total inability to undergo terminal differentiation. First, we found Lin28A
underexpressed in blast cells from AML patients and AML cell lines as compared
with CD34+ normal precursors. In vitro transfection of Lin28A in NPM1-mutated
OCI-AML3 cell line significantly triggered cell-cycle arrest and myeloid
differentiation, with increased expression of macrophage associate genes (EGR2,
ZFP36 and ANXA1). Furthermore, miR-128a, a negative regulator of Lin28A, was
found overexpressed in AML cells compared with normal precursors, especially in
acute promyelocytic leukemia (APL) and in ‘AML with maturation’ (according to
2016 WHO classification of myeloid neoplasms and acute leukemia). Its forced
overexpression by lentiviral infection in OCI-AML3 downregulated Lin28A with
ensuing repression of macrophage-oriented differentiation. Finally, knockdown
of miR-128a in OCI-AML3 and in APL/AML leukemic cells (by transfection and
lentiviral infection, respectively) induced myeloid cell differentiation and
increased expression of Lin28A, EGR2, ZFP36 and ANXA1, reverting myeloid
differentiation blockage. In conclusion, our findings revealed a new mechanism
for AML differentiation blockage, suggesting new strategies for AML therapy
based upon miR-128a inhibition.
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