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2.6 circFAT1 通过 miR⁃181d⁃5p/miR⁃199a⁃5p 调控 miR⁃199a⁃5p inhibitor 则相反（P < 0.05，图 6）；值得
PI3K/Akt/mTOR信号通路 注意的是 miR⁃181d⁃5p inhibitor 以及 miR⁃199a⁃5p
免疫印迹实验显示，siFAT1、miR⁃181d⁃5p mimic inhibitor 均可以部分逆转 siFAT1 抑制的 PI3K/Akt/
以及 miR⁃199a⁃5p mimic 抑制了 PI3K/Akt/mTOR 磷 mTOR 通路，而 miR⁃181d⁃5p mimic 以及 miR⁃199a⁃
酸化，而过表达 FAT1、miR⁃181d⁃5p inhibitor 以及 5p mimic 均部分减弱了过表达 FAT1 激活的 PI3K/

A HSC⁃3 B SCC⁃25 C HSC⁃3 D SCC⁃25

siNC+IC#1 siFAT1+IC#1 siFAT1+miR⁃ 181d⁃5p inhibitor siNC+miR⁃ 181d⁃5p inhibitor NC+MC#1 FAT1+MC#1 FAT1+miR⁃ mimic 181d⁃5p NC+miR⁃ mimic 181d⁃5p siNC+IC#2 siFAT1+IC#2 siFAT1+miR⁃ 199a⁃5p inhibitor siNC+miR⁃ 199a⁃5p inhibitor NC+MC#2 FAT1+MC#2 FAT1+miR⁃ mimic 199a⁃5p NC+miR⁃ mimic 199a⁃5p

P13K 85 kDa P13K 85 kDa P13K 85 kDa P13K 85 kDa
p⁃P13K 84 kDa p⁃P13K 84 kDa p⁃P13K 84 kDa p⁃P13K 84 kDa
Akt 55 kDa Akt 55 kDa Akt 55 kDa Akt 55 kDa
p⁃Akt 56 kDa p⁃Akt 56 kDa p⁃Akt 56 kDa p⁃Akt 56 kDa
mTOR 289 kDa mTOR 289 kDa mTOR 289 kDa mTOR 289 kDa
p⁃mTOR 289 kDa p⁃mTOR 289 kDa p⁃mTOR 289 kDa p⁃mTOR 289 kDa
GAPDH 2.0 36 kDa GAPDH 2.5 36 kDa GAPDH 2.0 36 kDa GAPDH 2.0 36 kDa
HSC⁃3中p⁃P13K/P13K 1.5 SCC⁃25中p⁃P13K/P13K 2.0 HSC⁃3中p⁃P13K/P13K 1.5 SCC⁃25中p⁃P13K/P13K 1.5

1.5
1.0
1.0
1.0
1.0
0.5
0.5
0.5
0.5
0.0
0.0
0.0
0.0
siNC+IC#2
siNC+miR⁃199a⁃5p inhibitor
NC+miR⁃181d⁃5p mimic
siNC+miR⁃181d⁃5p inhibitor
FAT1+MC#1
NC+MC#2
NC+miR⁃199a⁃5p mimic
FAT1+MC#2
siNC+IC#1
siFAT1+miR⁃181d⁃5p inhibitor FAT1+miR⁃181d⁃5p mimic siFAT1+miR⁃199a⁃5p inhibitor FAT1+miR⁃199a⁃5p mimic
siFAT1+IC#2
NC+MC#1
siFAT1+IC#1
3 4 3 1.5 1.5
HSC⁃3中p⁃Akt/Akt 2 1 SCC⁃25中p⁃Akt/Akt 2 1 HSC⁃3中p⁃Akt/Akt 1.0 SCC⁃25中p⁃Akt/Akt 1.0
0.5
0.5
0 NC+MC#1 0.0 NC+MC#2
0.0
0
NC+miR⁃199a⁃5p mimic
siNC+miR⁃199a⁃5p inhibitor
siNC+IC#1
siNC+miR⁃181d⁃5p inhibitor
siFAT1+IC#1
siFAT1+IC#2
siFAT1+miR⁃181d⁃5p inhibitor FAT1+miR⁃181d⁃5p mimic siFAT1+miR⁃199a⁃5p inhibitor FAT1+miR⁃199a⁃5p mimic
NC+miR⁃181d⁃5p mimic
FAT1+MC#1
FAT1+MC#2
siNC+IC#2
HSC⁃3中p⁃mTOR/mTOR 4 3 2 1 SCC⁃25中p⁃mTOR/mTOR 3 2 1 HSC⁃3中p⁃mTOR/mTOR 2.5 SCC⁃25中p⁃mTOR/mTOR 1.5
2.0
1.0
1.5
1.0
0.5
0.5
0.0
0
0.0
0
FAT1+MC#1
FAT1+MC#2
NC+MC#1
NC+miR⁃199a⁃5p mimic
siNC+IC#1
NC+miR⁃181d⁃5p mimic
siNC+miR⁃199a⁃5p inhibitor
siFAT1+miR⁃181d⁃5p inhibitor FAT1+miR⁃181d⁃5p mimic siFAT1+miR⁃199a⁃5p inhibitor FAT1+miR⁃199a⁃5p mimic
NC+MC#2
siFAT1+IC#2
siFAT1+IC#1
siNC+miR⁃181d⁃5p inhibitor
siNC+IC#2
A~D：PI3K/Akt/mTOR信号通路相关蛋白的免疫印迹及计量数据统计图。
图6 circFAT1通过miR⁃181d⁃5p/miR⁃199a⁃5p调控PI3K/Akt/mTOR信号通路
Figure 6 circFAT1 regulates PI3K/Akt/mTOR signaling pathway through miR⁃181d⁃5p/miR⁃199a⁃5p