Long Noncoding RNA ANRIL Promotes Cervical Cancer Development by Acting as a Sponge of miR-186.
Long Noncoding RNA ANRIL Promotes Cervical Cancer Development by Acting as a Sponge of miR-186.
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DOI：
10.3727/096504017x14953948675449
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发表时间：
2018-04-10
影响因子：
3.1
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Zhang JJ;Wang DD;Du CX;Wang Y
宫颈癌是女性生殖系统常见的恶性肿瘤。据报道，长链非编码RNA（lncRNA）在多种癌症中调节肿瘤进展。INK 4基因座中的lncRNA反义非编码RNA（ANRIL）已被确定为多种肿瘤中的致癌分子靶点;然而，涉及宫颈癌发生的功能和潜在机制仍不清楚。在本研究中，RT-PCR显示ANRIL表达在宫颈癌肿瘤和细胞系中显著上调。而ANRIL基因敲低转染干扰寡核苷酸后，抑制了宫颈癌细胞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试验预测并验证了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，并与ANRIL的表达水平呈负相关。此外，拯救实验表明miR-186抑制剂可以逆转ANRIL敲低的抑制。总之，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。
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.