MiR-20b, -21, and -130b inhibit PTEN expression resulting in B7-H1 over-expression in advanced colorectal cancer.
Co-inhibitor B7-H1 expresses in various cancers and contributes to cancer immune evasion by inhibiting T cell activation and proliferation, yet the regulatory mechanisms for B7-H1 over-expression in cancers remain largely unknown. Here, the expression of B7-H1 and PTEN proteins were firstly detected by using immunohistochemistry method. B7-H1 immunoreactivities were found in 54.5% (55/101) of the colorectal cancer tissues with no expression in the normal tissues, and the PTEN protein immunoreactivities were observed in 51.5% (52/101) of the colorectal cancer tissues and 72.3% (73/101) of the normal tissues. Statistical analysis results indicated that the B7-H1 expression was negatively correlated to the PTEN expression in colorectal cancer (p=0.001). Then the expressions of microRNAs (miRNAs) in six pairs of colorectal cancer and normal tissues were determined by miRNA array, and 30 up-regulated miRNAs were found in the colorectal cancer tissues. Finally, the impact of these up-regulated miRNAs on PTEN expression was tested by using dual-luciferase reporter assay system, from which the results indicated that miR-20b, -21, and -130b were involved in suppression of PTEN expression. These findings suggest that miR-20b, -21, and -130b, up-regulated in colorectal cancer, through inhibiting the expression of PTEN, result in B7-H1 over-expression in colorectal cancer.
Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, China; Laboratory of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
Jianjie
J
Zhu
Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Lanxin
L
Chen
Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, China.
Lingting
L
Zou
Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, China.
Panpan
P
Yang
Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, China.
Ruirong
R
Wu
Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, China.
Yong
Y
Mao
Department of Clinical Laboratory, The Fourth Affiliated Hospital of Soochow University, Wuxi, China.
Huan
H
Zhou
Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Rui
R
Li
Department of Orthopedic Medicine, Guizhou Orthopedics Hospital, Guiyang, China.
Kaicai
K
Wang
Center of Drug Metabolism and Pharmacokinetics, College of Pharmaceutical Sciences, Soochow University, Suzhou, China. Electronic address: wangweipeng@suda.edu.cn.
Weipeng
W
Wang
Department of Oncology, The Fourth Affiliated Hospital of Soochow University, Wuxi, China. Electronic address: huadong@csco.org.cn.
Dong
D
Hua
Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Xueguang
X
Zhang
D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference
D020413:3' Untranslated Regions; D060890:B7-H1 Antigen; C554019:MIRN130 microRNA, human; C534451:MIRN20a microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase