Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, China.
Hemodialysis Room, Linyi People's Hospital, Linyi, China.
J Cell Mol Med. 2020 Jun;24(11):6015-6027. doi: 10.1111/jcmm.15117. Epub 2020 Apr 21.
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.
宫颈癌是主要恶性肿瘤之一，其病理生理学和进展仍知之甚少。长链非编码 RNA（lncRNA）先前被认为与宫颈癌的进展有关。本研究旨在通过调节转录因子 E2F4 来确定 lncRNA 心和神经嵴衍生表达 2-反义 RNA 1（HAND2-AS1）是否通过调节 16 号染色体开放阅读框 74（C16orf74）来影响宫颈癌的发展。采用 RT-qPCR 检测宫颈癌细胞中 HAND2-AS1 的表达。然后，用 HAND2-AS1 或 si-E2F4 RNA 或 C16orf74 处理宫颈癌细胞，检测细胞增殖、集落形成、迁移和侵袭能力。此外，还探讨了 HAND2-AS1 与 E2F4 或 E2F4 与 C16orf74 之间的结合。最后，通过改变 HAND2-AS1/E2F4/C16orf74 表达的裸鼠检测宫颈癌细胞的致瘤性。HAND2-AS1 在宫颈癌中表达较差，过表达 HAND2-AS1 抑制宫颈癌细胞的增殖、集落形成、迁移和侵袭。此外，发现 HAND2-AS1 将转录因子 E2F4 募集到 C16orf74 启动子区域并下调 C16orf74 表达。最后，HAND2-AS1/E2F4/C16orf74 调节了裸鼠宫颈癌的发生。总之，本研究通过抑制转录因子 E2F4 抑制 C16orf74 的表达，为 HAND2-AS1 抑制宫颈癌发展提供了证据。本研究强调了 lncRNA HAND2-AS1 作为治疗宫颈癌的靶点的潜力。
