Am J Pathol 2011 Nov;179 (5): 2580-8. [IF:5.224]
miR-375 Is Down-Regulated in Squamous Cervical Cancer and Inhibits Cell Migration and Invasion via Targeting Transcription Factor SP1.
Wang F , Li Y , Zhou J , Xu J , Peng C , Ye F , Shen Y , Lu W , Wan X , Xie X .
Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
浙江省女性生殖健康重点实验室，浙江省妇女医院，浙江大学医学院
Abstract
Pelvic lymph node metastases are regarded as the most important risk factor and a predictor of poor prognosis for patients with cervical cancer. Exploration of metastasis-related molecules is helpful toward improving the prognosis in cervical cancer. To identify the role of miR-375 in metastasis and progression of cervical cancer, we examined the expression of miR-375 in 170 cervical cancer tissues and 68 normal cervical tissues, using stem-loop quantitative PCR, and found that the expression of miR-375 in cervical cancer tissues was significantly decreased by 4.45-fold, compared with 68 normal tissues. A significant correlation existed between miR-375 expression and clinicopathologic parameters, including lymph node metastasis of cervical cancer. Overexpressed miR-375 suppressed cell proliferation, blocked G1-to-S cell-cycle transition, and inhibited cell migration and invasion in human cervical SiHa and CaSki cells. SP1, a potential target gene of miR-375, was inversely correlated with miR-375 expression in cervical cancer tissues. Moreover, SP1 was negatively regulated by miR-375, and knockdown of SP1 by siRNA inhibited cell malignant behaviors. Thus, our findings suggest that down-regulated miR-375 promotes cell malignant behaviors via the target gene SP1 and may consequently contribute to the progression of cervical cancer.
摘要
盆腔淋巴结转移被视为预示宫颈癌预后不良最重要的危险因素。探索研究盆腔淋巴结转移相关分子有助于改善宫颈癌预后。为了评估miR-375在宫颈癌转移和进展的作用,我们使用定量PCR技术检测了170例宫颈癌组织和68例正常宫颈组织miR-375的表达情况。我们发现，与68例正常宫颈组织相比，宫颈癌组织miR-375的表达明显降低，达4.45倍。miR-375的表达和临床病理（宫颈癌淋巴结转移）之间存在着显著的关联。miR-375的过度表达能抑制细胞增殖,切断G1-to-S细胞信号传递通路,抑制细胞迁移和抑制宫颈（SiHa 和 CaSki）细胞的侵袭。SP1是miR-375一个潜在靶基因, SP1在宫颈癌组织中与miR-375的表达呈负相关。此外,SP1受到miR-375反向调节作用,通过siRNA 技术降低SP1的表达可以抑制恶性细胞侵袭行为。综上所述,我们的研究结果提示，在靶基因 SP1的调节下，miR-375在宫颈癌组织中表达下调会促进癌细胞的迁移和入侵，从而可能导致宫颈癌转移和进展。
