The epigenetically-regulated miR-34a targeting c-SRC suppresses RAF/MEK/ERK signaling pathway in K-562 cells

- miR-34a was down-regulated in K-562 and CML patients due to DNA hypermethylation.
- miR-34a was over expressed in K-562 cells with miR-34a lentiviruses infection.
- miR-34a regulated c-SRC gene by binding two sites in c-SRC 3′ UTR.
- miR-34a down-regulation resulted in c-SRC up-regulation in the CML patients.
- miR-34a suppressed the RAF/MEK/ERK signalling pathway by down-regulating c-SRC.

Previous reports show that miR-34a suppressed K-562 cell proliferation and contributed to megakaryocytic differentiation of K-562 cells. Here, we reported that miR-34a, a tumor suppressor gene, is down-regulated in the K-562 cells and chronic myeloid leukemia (CML) patients due to aberrant DNA hypermethylation. c-SRC is a target of miR-34a. Restoring miR-34a expression resulted in down-regulation of c-SRC and phosphorylated (Tyr416) c-SRC protein in K-562 cells, which consequently triggered suppression of the RAF/MEK/ERK signaling pathway to decrease cell proliferation.