Let-7a microRNA functions as a potential tumor suppressor in human laryngeal cancer.
MicroRNAs (miRNAs) are endogenously expressed non-coding RNAs, which are involved in the gene expression regulation. Lethal-7a (let-7a) is a founding member of miRNA family and recently it was found to be associated with several cancers, such as lung and colon cancers. In the present study, we found that let-7a miRNA expression was significantly downregulated both in human laryngeal squamous cancer tissues and in Hep-2 cells, a laryngeal cancer cell line, as compared with adjacent normal tissues and BEAS-2B cells, respectively. Moreover, we found that let-7a expression levels were significantly further decreased in non-differentiated (G3) cancer tissues as compared with moderately and well differentiated cancer tissues (G2 and G1), although no significant difference in let-7a expression levels between the cancer specimens with different T stages or specimens from patients with different lymph node metastasis status was revealed. In Hep-2 cells, let-7a mimics transfection markedly suppressed proliferation and induced apoptosis of Hep-2 cells under the treatment of diamminedichloroplatinum or not and downregulated RAS and c-MYC protein expression without affecting the mRNA levels. In parallel, RAS and c-MYC protein levels were found significantly upregulated only in cancer tissues with downregulated let-7a expression. Thus, we propose that let-7a may be a tumor suppressor in laryngeal cancer by inhibiting cell growth, inducing cell apoptosis and downregulating the oncogenes expression.
Long
Xiao-Bo
XB
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Sun
Guang-Bin
GB
Hu
Shuang
S
Liang
Geng-Tian
GT
Wang
Nan
N
Zhang
Xin-Hao
XH
Cao
Ping-Ping
PP
Zhen
Hong-Tao
HT
Cui
Yong-Hua
YH
Liu
Zheng
Z
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000556:secondary; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007830:Larynx / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; D018631:ras Proteins