Down-regulation of PTEN expression modulated by dysregulated miR-21 contributes to the progression of esophageal cancer.
OBJECTIVE
miR-21, a putative tumor oncomiR, is a frequently overexpressed miRNA in a variety of tumors. Because it targets tumor-suppressor genes it has been linked to tumor progression. In this study we investigated the role of miR-21 in esophageal squamous cell carcinoma (ESCC), and its possible mechanism.


METHODS
Expression of miR-21 was detected by stem-loop RT-PCR in tissue from 76 invasive ESCC at stage I-IV and in their corresponding para-cancerous histological normal tissues (PCHNT). Thirty endoscopic esophageal mucosal biopsy specimens from non-tumor patients were used as controls. Expression of PTEN in 76 paired ESCC and PCHNT was investigated by real-time RT-PCR and an immunohistochemical method, respectively. Paired tumor and PCHNT specimens of 20 ESCC cases were randomly selected for western blot analysis. The effect of miR-21 on PTEN expression was assessed in the ESCC cell line with an miR-21 inhibitor to reduce miR-21 expression. Furthermore, the roles of miR-21 in cell biology were analyzed by use of miR-21 inhibitor-transfected cells.


RESULTS
Stem-loop RT-PCR revealed miR-21 was significantly overexpressed in ESCC tissues and cell lines. Overexpression of miR-21 correlated with tumor status, lymph node metastasis, and clinical stage. We demonstrated that knockdown of miR-21 significantly increased expression of PTEN protein. Consequent PTEN expression reduced cell proliferation, invasion, and migration.


CONCLUSIONS
Our findings suggest that miR-21 could be a potential oncomiR, probably by regulation of PTEN, and a novel prognostic factor for ESCC patients.
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, People's Republic of China, lipeifreemai@zzu.edu.cn.
Pei
P
Li
Wei-Min
WM
Mao
Zhi-Guo
ZG
Zheng
Zi-Ming
ZM
Dong
Zhi-Qiang
ZQ
Ling
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D004947:Esophagus / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human