A novel hypoxia-induced miR-147a regulates cell proliferation through a positive feedback loop of stabilizing HIF-1α.
Hypoxia is a general event in solid tumor growth. Therefore, induced cellular responses by hypoxia are important for tumorigenesis and tumor growth. MicroRNAs (miRNAs) have recently emerged as important regulators of hypoxia induced cellular responses. Here we report that miR-147a is a novel and crucial hypoxia induced miRNA. HIF-1α up-regulates the expression of miR-147a, and miR-147a in turn stabilizes and accumulates HIF-1α protein via directly targeting HIF-3α, a dominant negative regulator of HIF-1α. Subsequent studies in xenograft mouse model reveal that miR-147a is capable of inhibiting tumor growth. Collectively, these data demonstrate a positive feedback loop between HIF-1α, miR-147a and HIF-3α, which provide a new insight into the mechanism of miR-147a induced cell proliferation arrest under hypoxia.
a School of Life Sciences , Tsinghua University , Beijing , P.R. China.|b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.
Fan
F
Wang
a School of Life Sciences , Tsinghua University , Beijing , P.R. China.|b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.
Haoxiang
H
Zhang
b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.
Naihan
N
Xu
a School of Life Sciences , Tsinghua University , Beijing , P.R. China.|b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.
Nunu
N
Huang
b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.|c Department of Chemistry , Tsinghua University , Beijing , P.R. China.
Caiming
C
Tian
b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.
Anlin
A
Ye
d Department of Medicine , UMass Medical School , Worcester , Massachusetts , USA.
Guangnan
G
Hu
b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.|e Department of Gastroenterology , Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University , Guangzhou , P.R. China.
Jie
J
He
b Key Lab in Healthy Science and Technology , Division of Life Science, Graduate School at Shenzhen, Tsinghua University , Shenzhen , P.R. China.|f Open FIESTA Center , Tsinghua University , Shenzhen , P.R. China.
Yaou
Y
Zhang
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D006367:HeLa Cells; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C550570:MIRN148 microRNA, human; D035683:MicroRNAs
Cell proliferation; HIF-1α; HIF-3α; miR-147a