Zhou You, Hao Yinghua, Li Yuxia, Li Ruizhen, Wu Ruifang, Wang Shubin, Fang Zhengyu
Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, Guangdong Province, 518036, China.
Department of Gynecology and Obstetrics, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.
BMC Cancer. 2017 Mar 29;17(1):230. doi: 10.1186/s12885-017-3201-0.
Cervical squamous cell carcinoma (CSCC) is the most frequent type among cervical cancers. Although the altered miRNA miR-30d expression and the amplified chromosome locus of MIR30D, 8q24, have been reported in somatic cancers, the definitive functional impact of such region especially in CSCC remains under-investigated.
One hundred thirty-six cases of CSCC tissues and matched adjacent normal ovarian epithelial tissues were assessed in this study. FISH and qPCR were performed to detect the copy number and microRNA expression of MIR30D gene in the collected samples. In in-vitro study, proliferation of CSCC cells were analyzed using WST-1 assay and invasion abilities of CSCC cells were evaluated by transwell assay. In-vivo study using a model of nude mice bearing tumor was also performed.
Copy number gains of MIR30D were detected in 22.8% (31 out of 136) of CSCC samples. Copy number of MIR30D was positively correlated with tumor progression. CSCCs with lymph node metastases (LNM) also showed more frequencies (36.4%) of MIR30D amplification than those without LNM (18.4%, p < 0.05). CSCCs with increased copy number of MIR30D also showed a positive correlation with miR-30d up-regulation. Inhibition of miR-30d in CSCC cells led to impaired tumor growth and migration.
Copy number amplifications of MIR30D gene and enhanced expression of miR-30d were positively correlated with tumor progression in CSCCs, indicating miR-30d might play an oncomiric role in the progression of CSCC.
宫颈鳞状细胞癌(CSCC)是宫颈癌中最常见的类型。尽管在实体癌中已报道了miRNA miR-30d表达改变以及MIR30D基因(位于8q24染色体位点)的扩增,但该区域尤其是在CSCC中的明确功能影响仍研究不足。
本研究评估了136例CSCC组织及配对的相邻正常卵巢上皮组织。采用荧光原位杂交(FISH)和定量聚合酶链反应(qPCR)检测所收集样本中MIR30D基因的拷贝数和微小RNA表达。在体外研究中,使用WST-1法分析CSCC细胞的增殖情况,并通过Transwell法评估CSCC细胞的侵袭能力。还进行了使用荷瘤裸鼠模型的体内研究。
在22.8%(136例中的31例)的CSCC样本中检测到MIR30D拷贝数增加。MIR30D的拷贝数与肿瘤进展呈正相关。有淋巴结转移(LNM)的CSCC中MIR30D扩增的频率(36.4%)也高于无LNM的CSCC(18.4%,p<0.05)。MIR30D拷贝数增加的CSCC也与miR-30d上调呈正相关。抑制CSCC细胞中的miR-30d导致肿瘤生长和迁移受损。
MIR30D基因的拷贝数扩增和miR-30d表达增强与CSCC的肿瘤进展呈正相关,表明miR-30d可能在CSCC进展中发挥癌基因作用。