The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L.
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.
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.|Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Shumin
S
Wang
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.|Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Yingxi
Y
Mo
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Kaoru
K
Midorikawa
Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Zhe
Z
Zhang
Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Guangwu
G
Huang
Faculty of Nursing Science, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Ning
N
Ma
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.|Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Weilin
W
Zhao
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Yusuke
Y
Hiraku
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Shinji
S
Oikawa
Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Mariko
M
Murata
D000818:Animals; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D014162:Transfection
C000591059:ANLN protein, human; D018840:HSP70 Heat-Shock Proteins; C490979:HSPA4L protein, human; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins
Epstein-Barr virus; biomarker; microRNA; nasopharyngeal carcinoma; tumor suppressor