Interference of the long noncoding RNA CDKN2B-AS1 upregulates miR-181a-5p/TGFβI axis to restrain the metastasis and promote apoptosis and senescence of cervical cancer cells.

CANCER MEDICINE(2019)

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摘要
Long noncoding RNA (lncRNA) CDKN2B-AS1 has been shown to play a crucial role in the development as well as in the prognosis of various human cancers, including cervical cancer. However, the underlying mechanisms need to be further explored between CDKN2B-AS1 and cervical cancer. In the present study, RT-PCR showed that the mRNA level of CDKN2B-AS1 was significantly upregulated while the miR-181a-5p was downregulated in cervical cancer cell lines. In addition, the interference of CDKN2B-AS1 by shRNA resulted in the suppression of cell proliferation, invasion, migration and promotion of apoptosis and senescence, and either CDKN2B-AS1 overexpression or miR-181a-5p showed reversed results. Further studies demonstrated that CDKN2B-AS1 could directly interact with miR-181a-5p, and that there was an inverse correlation between miR-181a-5p and CDKN2B-AS1. In addition, we found that TGF beta I was a target of miR-181a-5p and could be downregulated by CDKN2B-AS1 knockdown. Moreover, the in vivo experiments further demonstrated the contribution of CDKN2B-AS1 in cervical cancer including tumor growth, apoptosis inhibition and senescence inhibition, and CDKN2B-AS1 knockdown could inhibit the aforementioned activities. In summary, our study demonstrated that the CDKN2B-AS1/miR-181a-5p/TGF beta I axis might play a vital role in cervical cancer development.
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关键词
CDKN2B-AS1,cervical cancer,epithelial-mesenchymal transition,senescence
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