期刊
ONCOTARGET
卷 6, 期 34, 页码 35893-35907出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5651
关键词
nasopharyngeal carcinoma; microRNA; Epstein-Barr virus; tumor suppressor; biomarker
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [22406016, 25305020, 25293149]
- Program for New Century Excellent Talents in University [NCET-12-0654]
- Guangxi Natural Science Foundation [2013GXNSFGA019002]
- Grants-in-Aid for Scientific Research [25670313, 24390172, 15K15235, 26460813, 26293148, 15H04784, 25293149, 22406016, 15K15237, 25305020] Funding Source: KAKEN
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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