MicroRNA 135a suppresses lymph node metastasis through down-regulation of ROCK1 in early gastric cancer.
MicroRNAs (miRNAs) play a critical role in gastric cancer progression and metastasis. This study investigated the role of miRNA-135a in early gastric cancer (EGC) including lymph node (LN) metastasis. We examined the correlation between miRNA-135a expression and clinical outcomes in 59 patients who underwent surgery for EGC. Using gastric cancer cell lines, we performed functional and target gene analyses. miRNA-135a expression was down-regulated in 33.9% of patients. These patients showed a significantly more advanced stage (TNM stage ≥ IB, 35.0% vs. 12.8%, p = 0.045) and higher rate of LN metastasis (30.0% vs. 5.1%, p = 0.014) than those with up-regulation of miRNA-135a expression. In a multivariate analysis, down-regulation of miRNA-135a was an independent risk factor for LN metastasis (adjusted odds ratio, 8.04; 95% confidence interval, 1.08-59.81; p = 0.042). Functional analyses using gastric cancer cell lines showed that miRNA-135a suppressed cell viability, epithelial-mesenchymal transition, cell invasion, and migration. ROCK1 was a target of miRNA-135a and its expression was inversely correlated to that of miRNA-135a. ROCK1 expression was significantly increased in EGC patients with LN metastasis than in those without LN metastasis. Our results confirm the tumor-suppressive role of miRNA-135a, and demonstrate its role in LN metastasis in EGC. miRNA-135a and its target gene ROCK1 may be novel therapeutic and prognostic targets for EGC.
Center for Gastric Cancer, National Cancer Center, Goyang, Korea ; Department of life Science and Biotechnology, Paichai University, Daejeon, Korea.
Ji-Young
JY
Shin
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Young-Il
YI
Kim
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Soo-Jeong
SJ
Cho
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Mi Kyung
MK
Lee
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Myeong-Cherl
MC
Kook
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Jun Ho
JH
Lee
Department of life Science and Biotechnology, Paichai University, Daejeon, Korea.
Sang Soo
SS
Lee
Departments of Medicine, Howard University, Washington, District of Columbia, United States of America.
Hassan
H
Ashktorab
Departments of Medicine, Howard University, Washington, District of Columbia, United States of America.
Duane T
DT
Smoot
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Keun Won
KW
Ryu
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Young-Woo
YW
Kim
Center for Gastric Cancer, National Cancer Center, Goyang, Korea.
Il Ju
IJ
Choi
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000368:Aged; D018279:Carcinoma, Signet Ring Cell / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D042241:Early Diagnosis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
C544965:MIRN135 microRNA, human; D035683:MicroRNAs; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases