Department of Obstetrics and Gynecology, The First Affiliated Hospital of Henan University of Science and TechnologyLuoyang, Henan ProvinceP.R. China.
Department of Obstetrics, Peoples Hospital of Zhengzhou UniversityZhengzhou, Henan ProvinceP.R. China.
Oncol Res. 2018 Apr 10;26(3):345-352. doi: 10.3727/096504017X14953948675449. Epub 2017 May 22.
Cervical cancer is a common malignancy of the female reproductive system. Long noncoding RNAs (lncRNAs) have been reported to modulate tumor progression in multiple cancers. The lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) has been identified as an oncogenic molecular target in several tumors; however, the function and underlying mechanism involved in cervical cancer oncogenesis are still unclear. In the present study, RT-PCR showed that ANRIL expression was significantly upregulated in cervical cancer tumors and cell lines. Nevertheless, ANRIL knockdown transfected with interference oligonucleotide inhibited the proliferation activity and invasive ability, and promoted apoptosis of cervical cancer cell lines. The bioinformatics prediction program and luciferase assay predicted and validated that miR-186 directly targeted ANRIL. The expression level of miR-186 was downregulated in cervical cancer tumors and cell lines and was negatively correlated to that of ANRIL. Moreover, rescue experiments showed that miR-186 inhibitor could reverse the suppression of ANRIL knockdown. In summary, our study demonstrated that the ANRIL/miR-186 axis might play a vital role in cervical cancer tumorigenesis.
宫颈癌是女性生殖系统常见的恶性肿瘤。长链非编码 RNA（lncRNA）已被报道在多种癌症中调节肿瘤进展。INK4 基因座反义非编码 RNA（ANRIL）已被确定为多种肿瘤中的致癌分子靶标；然而，其在宫颈癌发生中的功能和潜在机制仍不清楚。在本研究中，RT-PCR 显示 ANRIL 在宫颈癌肿瘤和细胞系中表达显著上调。然而，用干扰寡核苷酸转染的 ANRIL 敲低抑制了宫颈癌细胞系的增殖活性和侵袭能力，并促进了细胞凋亡。生物信息学预测程序和荧光素酶测定预测并验证了 miR-186 直接靶向 ANRIL。miR-186 在宫颈癌肿瘤和细胞系中的表达水平下调，与 ANRIL 的表达呈负相关。此外，挽救实验表明，miR-186 抑制剂可以逆转 ANRIL 敲低的抑制作用。综上所述，我们的研究表明，ANRIL/miR-186 轴可能在宫颈癌肿瘤发生中发挥重要作用。
