miR-483-5p promotes invasion and metastasis of lung adenocarcinoma by targeting RhoGDI1 and ALCAM.
The nodal regulatory properties of microRNAs (miRNA) in metastatic cancer may offer new targets for therapeutic control. Here, we report that upregulation of miR-483-5p is correlated with the progression of human lung adenocarcinoma. miR-483-5p promotes the epithelial-mesenchymal transition (EMT) accompanied by invasive and metastatic properties of lung adenocarcinoma. Mechanistically, miR-483-5p is activated by the WNT/β-catenin signaling pathway and exerts its prometastatic function by directly targeting the Rho GDP dissociation inhibitor alpha (RhoGDI1) and activated leukocyte cell adhesion molecule (ALCAM), two putative metastasis suppressors. Furthermore, we found that downregulation of RhoGDI1 enhances expression of Snail, thereby promoting EMT. Importantly, miR-483-5p levels are positively correlated with β-catenin expression, but are negatively correlated with the levels of RhoGDI1 and ALCAM in human lung adenocarcinoma. Our findings reveal that miR-483-5p is a critical β-catenin-activated prometastatic miRNA and a negative regulator of the metastasis suppressors RhoGDI1 and ALCAM.
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Qiancheng
Q
Song
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Yuanfei
Y
Xu
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Cuilan
C
Yang
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Zhenguo
Z
Chen
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Chunhong
C
Jia
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Juan
J
Chen
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Yue
Y
Zhang
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Pinglin
P
Lai
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Xiaorong
X
Fan
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Xuan
X
Zhou
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Jun
J
Lin
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Ming
M
Li
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Wenli
W
Ma
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China.
Shenqiu
S
Luo
Authors' Affiliations: Department of Cell Biology, School of Basic Medical Sciences; and Institute of Genetic Engineering, Southern Medical University, Guangzhou, China baixc15@smu.edu.cn.
Xiaochun
X
Bai
D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D018450:Disease Progression; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D005326:Fetal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000235:genetics* / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule
D020413:3' Untranslated Regions; D015703:Antigens, CD; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; D035683:MicroRNAs; D051176:beta Catenin; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C548912:MIRN483 microRNA, human