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LncRNA HAND2-AS1 represses cervical cancer progression by interaction with transcription factor E2F4 at the promoter
Junling Gong1, Haiying Fan2, Jing Deng3
1Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, China.
Abstract:
Cervical cancer is one of the major malignancies, the pathophysiology and progression of which remain to be scarcely understood. Long non-coding RNAs (lncRNAs) have been previously implicated in the progression of cervical cancer. Here, the purpose of this study was to identify whether lncRNA heart- and neural crest derivative-expressed 2-antisense RNA 1 (HAND2-AS1) affect the development of cervical cancer through regulation of chromosome 16 open reading frame 74 (C16orf74) by mediating a transcription factor E2F4. RT-qPCR was performed to determine the expression of HAND2-AS1 in cervical cancer cells. Then, cervical cancer cells were treated with HAND2-AS1 or si-E2F4 RNA, or C16orf74, after which the proliferation, colony formation, migration and invasion were detected. Moreover, the binding between HAND2-AS1 and E2F4 or between E2F4 and C16orf74 was explored. Finally, the tumorigenesis of cervical cancer cells was measured in nude mice with altered HAND2-AS1/E2F4/C16orf74 expression. HAND2-AS1 exhibited poor expression in cervical cancer, and HAND2-AS1 overexpression suppressed the proliferation, colony formation, migration and invasion of cervical cancer cells. In addition, HAND2-AS1 was found to recruit transcription factor E2F4 to C16orf74 promoter region and down-regulate C16orf74 expression. Lastly, HAND2-AS1/E2F4/C16orf74 modulated the tumorigenesis of cervical cancer in nude mice. In conclusion, this study provided evidence on the inhibitory effect of HAND2-AS1 on the development of cervical cancer through the suppression of C16orf74 expression by recruiting transcription factor E2F4. This study highlights the potential of lncRNA HAND2-AS1 as a target in the treatment of cervical cancer.
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