Dong Jing, Sui Long, Wang Qing, Chen Mingjun, Sun Hong
Department of Gynecology, Obstetrics and Gynecology Hospital, Shanghai Medical College, Fudan University, Shanghai 200011, P.R. China.
Mol Med Rep. 2014 Sep;10(3):1426-32. doi: 10.3892/mmr.2014.2335. Epub 2014 Jun 16.
The downregulation of microRNA‑26a (miR‑26a) has been reported in numerous types of cancer, but its detailed functional role in cervical cancer is not yet clear. In the present study, the expression of miR‑26a in human cervical cancer was confirmed and its contribution to cervical cancer progression was investigated. The expression of miR‑26a was determined by reverse transcription quantitative polymerase chain reaction in human cervical tissues and cell lines. Cell growth and invasion were detected by cell counting kit‑8, colony‑forming assays and transwell assays following restoration of miR‑26a expression. Protein tyrosine phosphatase type IVA 1 (PRL‑1) was further validated as a target of miR‑26a by a functional luciferase assay and western blot analysis. In addition, the overexpression of miR‑26a in tumor formation in SCID mice was investigated in vivo, and the association between miR‑26a and PRL‑1 was assayed by Pearson's correlation coefficient. First, it was identified that miR‑26a was significantly downregulated in cervical cancer compared with the paired adjacent tissues. Forced expression of miR‑26a suppressed cell proliferation and invasion in vitro and inhibited the growth of tumor xenografts in vivo. PRL‑1 was determined as a novel target for miR‑26a and knockdown of PRL‑1 partially phenocopied the effect of miR‑26a restoration. In addition, PRL‑1 expression was inversely correlated with miR‑26a expression in cervical cancer tissues. In conclusion, the results demonstrated the role of miR‑26a in cervical cancer pathogenesis and suggest it may be used as a potential novel therapeutic strategy for cervical cancer.
已有报道称，多种癌症中均存在微小RNA-26a（miR-26a）表达下调的情况，但其在宫颈癌中的具体功能作用尚不清楚。在本研究中，证实了miR-26a在人宫颈癌中的表达，并研究了其对宫颈癌进展的作用。通过逆转录定量聚合酶链反应测定人宫颈组织和细胞系中miR-26a的表达。在恢复miR-26a表达后，采用细胞计数试剂盒-8、集落形成试验和Transwell试验检测细胞生长和侵袭情况。通过功能性荧光素酶试验和蛋白质印迹分析进一步验证蛋白酪氨酸磷酸酶IVA1型（PRL-1）是miR-26a的靶标。此外，在体内研究了miR-26a在SCID小鼠肿瘤形成中的过表达情况，并通过Pearson相关系数分析了miR-26a与PRL-1之间的关联。首先，发现与配对的相邻组织相比，宫颈癌中miR-26a显著下调。miR-26a的强制表达在体外抑制细胞增殖和侵袭，并在体内抑制肿瘤异种移植物的生长。确定PRL-1是miR-26a的新靶标，敲低PRL-1部分模拟了miR-26a恢复的效果。此外，宫颈癌组织中PRL-1的表达与miR-26a的表达呈负相关。总之，结果证明了miR-26a在宫颈癌发病机制中的作用，并表明它可能作为宫颈癌潜在的新型治疗策略。
