Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma
Tumor suppressive microRNA-375 regulates lactate dehydrogenase B in maxillary sinus squamous cell carcinoma
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DOI：
10.3892/ijo.2011.1196
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发表时间：
2012-01-01
影响因子：
5.2
通讯作者：
Seki, Naohiko
中科院分区：
文献类型：
--
作者：
Kinoshita, Takashi;Nohata, Nijiro;Seki, Naohiko
microRNA-375（miR-375）在上颌窦鳞状细胞癌（MSSCC）组织中的表达显著降低。本研究的目的是研究miR-375的功能意义以及在MSSCC网络中可能的调节作用。在IMC-3细胞中，miR-375的恢复显著抑制癌细胞增殖和侵袭，表明miR-375在MSSCC中起肿瘤抑制剂的作用。全基因组基因表达数据和荧光素酶报告基因分析表明，乳酸脱氢酶B（LDHB）直接受miR-375调控。转染si-LDHB的IMC-3细胞对癌细胞的增殖和侵袭有明显的抑制作用，提示LDHB可能在MSSCC的致瘤功能中发挥作用。在临床MSSCC标本中，LDHB mRNA水平在癌组织中上调，其与miR-375的表达呈负相关。此外，Kaplan-Meier曲线和log-rank检验显示LDHB的高表达水平对生存率有显著的不利影响。对miR-375肿瘤抑制因子调控的癌症网络的鉴定可以为MSSCC肿瘤发生的分子机制提供新的见解。
The expression of microRNA-375 (miR-375) is significantly reduced in cancer tissues of maxillary sinus squamous cell carcinoma (MSSCC). The aim of this study was to investigate the functional significance of miR-375 and a possible regulatory role in the MSSCC networks. Restoration of miR-375 significantly inhibited cancer cell proliferation and invasion in IMC-3 cells, suggesting that miR-375 functions as a tumor suppressor in MSSCC. Genome-wide gene expression data and luciferase reporter assays indicated that lactate dehydrogenase B (LDHB) was directly regulated by miR-375. Cancer cell proliferation and invasion were significantly inhibited by transfection of si-LDHB into IMC-3 cells, suggesting that LDHB may play a role in MSSCC oncogenic function. In clinical MSSCC specimens, LDHB mRNA levels were up-regulated in cancer tissues, which were inversely correlated with the expression of miR-375. In addition, Kaplan-Meier curves and log-rank tests revealed that the high mRNA expression levels of LDHB had a significant adverse effect on survival rate. The identification of a cancer network regulated by the miR-375 tumor suppressor could provide new insights into the molecular mechanisms of MSSCC oncogenesis.