The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L
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Shumin Wang1,2, Yingxi Mo1,2, Kaoru Midorikawa1, Zhe Zhang2, Guangwu Huang2, Ning Ma3, Weilin Zhao1,2, Yusuke Hiraku1, Shinji Oikawa1, Mariko Murata1
1Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan
2Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
3Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie, Japan
Mariko Murata, e-mail: firstname.lastname@example.org
Keywords: nasopharyngeal carcinoma, microRNA, Epstein-Barr virus, tumor suppressor, biomarker
Received: July 03, 2015 Accepted: October 02, 2015 Published: October 14, 2015
Nasopharyngeal carcinoma (NPC) is a malignancy with poor prognosis that is endemic to Southeast Asia. We profiled microRNAs (miRNAs) of NPCs using microarrays and confirmed the results by quantitative RT-PCR. The results revealed that seven miRNAs were significantly up-regulated, and six miRNAs were down-regulated, in NPC tissues relative to noncancerous nasopharyngeal epithelia (NNE). Expression of miR-497 was also significantly reduced in the plasma of NPC patients relative to the plasma of noncancerous control patients. The concordant down-regulation of miR-497 in tissues and plasma suggested that miR-497 could be used as a diagnostic biomarker for NPC. Functional analyses of the effect of miR-497 on cancer phenotypes revealed that transfection of miR-497 mimic into NPC cells suppressed cell growth and migration and induced apoptosis. Subcutaneous xenografts of transfected cells in nude mice demonstrated that miR-497 significantly inhibited tumor growth. Two potential targets of miR-497, ANLN (anillin, actin-binding protein) and HSPA4L (heat shock 70 kDa protein 4–like), both of which were overexpressed in NPC tissues, were negatively regulated by miR-497 mimic in NPC cell lines. Silencing of ANLN and HSPA4L suppressed cell proliferation and migration and induced apoptosis in NPC cells. Our findings indicate that miR-497 is a potent tumor suppressor that inhibits cancer phenotypes by targeting ANLN and HSPA4L in NPC.
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