Long Xiao-Bo, Sun Guang-Bin, Hu Shuang, Liang Geng-Tian, Wang Nan, Zhang Xin-Hao, Cao Ping-Ping, Zhen Hong-Tao, Cui Yong-Hua, Liu Zheng
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Oncol Rep. 2009 Nov;22(5):1189-95. doi: 10.3892/or_00000554.
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.
微小RNA（miRNA）是内源性表达的非编码RNA，参与基因表达调控。致死-7a（let-7a）是miRNA家族的创始成员，最近发现它与多种癌症有关，如肺癌和结肠癌。在本研究中，我们发现与相邻正常组织和BEAS-2B细胞相比，let-7a miRNA在人喉鳞状癌组织和喉癌细胞系Hep-2细胞中的表达均显著下调。此外，我们发现与中分化和高分化癌组织（G2和G1）相比，未分化（G3）癌组织中let-7a的表达水平进一步显著降低，尽管不同T分期的癌标本或不同淋巴结转移状态患者的标本之间let-7a表达水平没有显著差异。在Hep-2细胞中，转染let-7a模拟物在顺铂处理或未处理的情况下均显著抑制Hep-2细胞的增殖并诱导其凋亡，下调RAS和c-MYC蛋白表达，而不影响mRNA水平。同时，仅在let-7a表达下调的癌组织中发现RAS和c-MYC蛋白水平显著上调。因此，我们认为let-7a可能通过抑制细胞生长、诱导细胞凋亡和下调癌基因表达而成为喉癌中的一种肿瘤抑制因子。
