The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L

• DOI: 10.18632/oncotarget.5651
• Publication Date: 2015-10-19T01:26:06Z
• Authors: Shumin Wang; Yingxi Mo; Kaoru Midorikawa; Zhe Zhang; Guangwu Huang; Ning Ma; Weilin Zhao; Yusuke Hiraku; Shinji Oikawa; Mariko Murata
• Keywords: Male; Mice, Inbred BALB C; Nasopharyngeal Carcinoma; Carcinoma; Microfilament Proteins; Mice, Nude; Nasopharyngeal Neoplasms; Middle Aged; Prognosis; Transfection; 3. Good health; Mice; MicroRNAs; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Cell Line, Tumor; Animals; Heterografts; Humans; Female; HSP70 Heat-Shock Proteins; Cell Proliferation

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.