Yang Y, Xie Y J, Xu Q, Chen J X, Shan N C, Zhang Y
School of Resources Processing and Bioengineering, Central South University, Changsha, China.
Xinjiang Cancer Hospital, Urumchi, China.
Gynecol Oncol. 2015 Sep;138(3):683-8. doi: 10.1016/j.ygyno.2015.06.015. Epub 2015 Jun 11.
MicroRNAs (miRNAs) are non-coding RNAs that regulate the expression of mRNAs by binding to their 3'-untranslated regions (UTRs). Accumulating evidences show that miRNAs are involved in tumorigenesis such as lung cancer, liver cancer, colon cancer, and cervical cancer. In this study, we focused on the expression of miR-1246 in clinical cervical cancer tissues as well as the relationship between miR-1246 and HPV16E6 infection status.
Real-time quantitative polymerase chain reaction technology was used to detect the expression of miR-1246 in 68 cervical cancer tissues and 52 normal tissues. The expression of miR-1246 also was tested in HPV16E6 negative cervical cell line (SiHa) or HPV16E6 positive cell line (C33A). Western blot was performed to detect the expression of DYRK1A after knocking down HPV16E6.
Our data showed that the expression of miR-1246 was dramatically decreased in cervical cancer tissue, compared with normal control group (p=0.0012), and miR-1246 was negatively correlated with clinical stage and HPV16E6 infected status (p=0.0410), but no correlation was observed with age, tumor diameter, cervical invasion depth, lymph node metastasis, or vascular invasion (p>0.05). Knock down of HPV16E6 significantly raised DYRK1A protein expression targeted by miR-1246.
The expression of miR-1246 is negatively correlated with cervical cancer procedure as well as HPV16E6 infection status and the miR-1246 may act as a diagnostic biomarker for cervical cancer. In addition, HPV16E6 infection may be a major reason leading to decrease the expression of miR-1246 in cervical cancer. This finding contributes to deep understanding of the miR-1246 function in cervical carcinogenesis.
微小RNA（miRNA）是非编码RNA，通过与mRNA的3'非翻译区（UTR）结合来调节mRNA的表达。越来越多的证据表明，miRNA参与肺癌、肝癌、结肠癌和宫颈癌等肿瘤的发生。在本研究中，我们重点关注miR-1246在临床宫颈癌组织中的表达以及miR-1246与HPV16E6感染状态之间的关系。
采用实时定量聚合酶链反应技术检测68例宫颈癌组织和52例正常组织中miR-1246的表达。还在HPV16E6阴性宫颈癌细胞系（SiHa）或HPV16E6阳性细胞系（C33A）中检测了miR-1246的表达。在敲低HPV16E6后，进行蛋白质免疫印迹法检测双特异性酪氨酸磷酸化调节激酶1A（DYRK1A）的表达。
我们的数据显示，与正常对照组相比，宫颈癌组织中miR-1246的表达显著降低（p = 0.0012），并且miR-1246与临床分期和HPV16E6感染状态呈负相关（p = 0.0410），但与年龄、肿瘤直径、宫颈浸润深度、淋巴结转移或血管浸润均无相关性（p>0.05）。敲低HPV16E6显著提高了miR-1246靶向的DYRK1A蛋白表达。
miR-1246的表达与宫颈癌进程以及HPV16E6感染状态呈负相关，miR-1246可能作为宫颈癌的诊断生物标志物。此外，HPV16E6感染可能是导致宫颈癌中miR-1246表达降低的主要原因。这一发现有助于深入了解miR-1246在宫颈癌发生中的作用。
