miR-101 represses lung cancer by inhibiting interaction of fibroblasts and cancer cells by down-regulating CXCL12.
Cancer-associated fibroblasts (CAFs) are the main component of tumor stroma which support tumor progression. Here, we set out to determine the factors that may be involved in dramatic alteration of microRNAs (miRNAs) expression pattern in CAFs. miRNAs analyses identified differential expression of 15 microRNAs, with miR-101 being the most downregulated miRNA in CAFs which were different from the normal fibroblasts. We examined several putative miR-101 target genes identified by microarray analysis and demonstrated that miR-101 directly targets CXCL12, which play important roles in CAFs. Overexpression of miR-101 significantly impaired the ability of CAFs to stimulate tumor cell proliferation, sphere formation migration and invasion, and enhanced apoptosis. Further research showed that the cellular biological behavior was regulated by miR-101 targeting CXCL12. These findings provide new insights miR-101 down-regulation in CAFs could inhibit lung cancer proliferation and metastasis via targeting CXCL12.
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jian
J
Zhang
Infectious Disease Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Jing
J
Liu
Department of Pathology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yong
Y
Liu
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Weibin
W
Wu
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Xiaojun
X
Li
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Yonghui
Y
Wu
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Huiguo
H
Chen
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Kai
K
Zhang
Thoracic Surgery Department, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: lijia_gu@126.com.
Lijia
L
Gu
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D054377:Chemokine CXCL12 / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D046228:Microarray Analysis; D009361:Neoplasm Invasiveness / Q000235:genetics
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C534072:MIRN101 microRNA, human; D035683:MicroRNAs
CAFs; CXCL12; Lung cancer; miR-101