Intronic miR-301 feedback regulates its host gene, ska2, in A549 cells by targeting MEOX2 to affect ERK/CREB pathways.
miR-301 is localized in the first intron of ska2, whose function has not been clarified. Here, a new circuit model in which intronic miR-301 regulates the transcription and function of its host gene through a feedback mechanism has been described. Our results showed that blocking of miR-301 in A549 cells leads to a decrease in the expression of the host gene, ska2. Further analysis showed that miR-301 targets MEOX2 to affect the ERK/CREB pathway. CREB directly regulates the expression of the host gene, ska2. In addition, the inhibition of miR-301 or ska2 resulted in an increase of the mitotic index and a decrease in colony formation in soft agar, which may be related to lung tumorigenesis.
Cao
Guojun
G
Beijing Institute of Basic Medical Sciences, No. 27 Taiping Road, Beijing 100850, China.
Huang
Baochun
B
Liu
Zhaohui
Z
Zhang
Jiyan
J
Xu
Hua
H
Xia
Wei
W
Li
Jie
J
Li
Shaohua
S
Chen
Liucun
L
Ding
Hongmei
H
Zhao
Qiang
Q
Fan
Ming
M
Shen
Beifen
B
Shao
Ningsheng
N
D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007438:Introns; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics
D002868:Chromosomal Proteins, Non-Histone; D017362:Cyclic AMP Response Element-Binding Protein; D018398:Homeodomain Proteins; C484193:MEOX2 protein, human; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; C516428:SKA2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases