Up-regulation of miR-187 modulates the advances of oral carcinoma by targeting BARX2 tumor suppressor
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Shu-Chun Lin1,3, Shou-Yen Kao1,3, Jennifer Chen-Yu Chang1, Ying-Chieh Liu1, En-Hao Yu2, Ssu-Hsueh Tseng1, Chung-Ji Liu2,4, Kuo-Wei Chang1,3
1Institute of Oral Biology, National Yang-Ming University, Taipei, Taiwan
2Department of Dentistry, School of Dentistry, National Yang-Ming University, Taipei, Taiwan
3Department of Stomatology, Taipei Veterans General Hospital, Taipei, Taiwan
4Department of Dentistry, MacKay Memorial Hospital, Taipei, Taiwan
Kuo-Wei Chang, email: [email protected]
Chung-Ji Liu, email: [email protected]
Keywords: BARX2, carcinoma, invasion, metastasis, miR-187
Received: March 02, 2016 Accepted: August 09, 2016 Published: August 17, 2016
Oral squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. Aberrations in miRNA regulation are known to play important roles in OSCC pathogenesis. miR-187 was shown to be up-regulated in head and neck malignancies in our previous screening. This study further investigated the oncogenic potential, clinical implications, and targets of miR-187 in OSCC. We observed that miR-187 increased oncogenicity, particularly migration, of OSCC cells. miR-187 expression increased the xenografic tumorigenicity and metastasis in mice. In addition, metastatic human OSCC had higher miR-187 expression than did non-metastatic tumors. Through vigorous screening, we confirmed BarH-like Homeobox 2 (BARX2) gene as an miR-187 target. BARX2 expression suppressed the migration, invasion, anchorage-independent colony formation, and orthotopic tumorigenesis of OSCC cells. The migratory phenotype and neck metastasis induced by miR-187 was rescued by BARX2 expression. BARX2 expression was down-regulated in the vast majority of OSCC, and this down-regulation was particularly conspicuous in tumors with advanced nodal metastasis. In addition, plasma miR-187 was significantly higher in OSCC patients than in normal individuals. This study highlights the roles of miR-187-BARX2 in driving the carcinogenesis of OSCC. The results suggest that miR-187 is a potential serological marker for OSCC and that targeting of miR-187 might prove effective in attenuating nodal metastasis.
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