The epigenetically-regulated miR-34a targeting c-SRC suppresses RAF/MEK/ERK signaling pathway in K-562 cells.
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.
Department of Hematology, Chinese PLA Air Force General Hospital, 30 Fucheng Road, Beijing 100042, China.
Yang
Y
Yang
Department of Hematology, Chinese PLA Air Force General Hospital, 30 Fucheng Road, Beijing 100042, China.
Li
L
Ding
Beijing Institute of Radiation Medicine, Chinese PLA Academy of Military Medical Science, Beijing 100850, China.
Zi-Kuan
ZK
Guo
Department of Hematology, Chinese PLA Air Force General Hospital, 30 Fucheng Road, Beijing 100042, China.
Xiao-Li
XL
Zheng
Beijing Institute of Radiation Medicine, Chinese PLA Academy of Military Medical Science, Beijing 100850, China.
Li-Sheng
LS
Wang
Beijing Institute of Radiation Medicine, Chinese PLA Academy of Military Medical Science, Beijing 100850, China.
Hui-Yan
HY
Sun
Aerospace Balance Medical Center, Chinese PLA Air Force General Hospital, Beijing 100042, China.
Zhan-Guo
ZG
Jin
Department of Hematology, Chinese PLA Air Force General Hospital, 30 Fucheng Road, Beijing 100042, China. Electronic address: wanghengxiang123@aliyun.com.
Heng-Xiang
HX
Wang
D000081247:CSK Tyrosine-Protein Kinase; D049109:Cell Proliferation; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D035683:MicroRNAs / Q000502:physiology*; D010766:Phosphorylation; D048490:raf Kinases / Q000378:metabolism*; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human; D048490:raf Kinases
Epigenetic; Methylation; c-SRC; miR-34a