Cervical cancer is a common cause of cancer-related mortality in women. Mounting evidence suggests that long non-coding RNAs (lncRNAs) function vitally in many cancers. In this study, we discovered that the regulation of the heart and neural crest derivatives expressed 2-antisense RNA 1 (HAND2-AS1) in cervical cancer. RT-qPCR was conducted to detect the expression of HAND2-AS1 and microRNA-21-5p (miR-21-5p). The relationship of HAND2-AS1 and miR-21-5p was identified by dual-luciferase reporter gene assay. The roles of HAND2-AS1, miR-21-5p and tissue inhibitor of metalloproteinases-3 (TIMP3) in cervical cancer were accessed via gain- and loss-of-function approaches. The expression of related proteins in the vascular endothelial growth factor A (VEGFA) signaling pathway was detected through Western blot analysis. Finally, xenografts of cervical cancer in nude mice were established to assess the effect of HAND2-AS1 on tumorigenesis in vivo. HAND2-AS1 and TIMP3 were downregulated in cervical cancer, which were identified to be associated with a poor prognosis of patients with cervical cancer. Moreover, HAND2-AS1 was upregulated the expression of TIMP3 through competitively binding to miR-21-5p. Overexpressed HAND2-AS1 or downregulated miR-21-5p inhibited cell proliferation, migration, and invasion while promoting cell apoptosis, in association with increased expression of proteins in VEGFA signaling pathway. These changes were reversed by silencing of TIMP3. Overexpressed HAND2-AS1 reduced the tumor formation ability in nude mice. In summary, HAND2-AS1 may exert inhibitory effects on cervical cancer cell growth and cervical cancer development through its regulation on the miR-21-5p/TIMP3/VEGFA axis. This highlights that HAND2-AS1 may serve as a potential target for cervical cancer diagnosis and treatment.

宫颈癌是女性癌症相关死亡的常见原因。越来越多的证据表明，长链非编码 RNA (lncRNA) 在许多癌症中发挥着至关重要的作用。在这项研究中，我们发现心脏和神经嵴衍生物的调控在宫颈癌中表达 2-反义 RNA 1 (HAND2-AS1)。进行 RT-qPCR 以检测 HAND2-AS1 和 microRNA-21-5p (miR-21-5p) 的表达。HAND2-AS1与miR-21-5p的关系通过双荧光素酶报告基因检测进行鉴定。HAND2-AS1、miR-21-5p 和金属蛋白酶组织抑制剂 3 (TIMP3) 在宫颈癌中的作用是通过获得和丧失功能的方法获得的。通过Western blot分析检测血管内皮生长因子A（VEGFA）信号通路相关蛋白的表达。最后，建立裸鼠宫颈癌异种移植物以评估 HAND2-AS1 对体内肿瘤发生的影响。HAND2-AS1 和 TIMP3 在宫颈癌中表达下调，这与宫颈癌患者预后不良有关。此外，HAND2-AS1 通过竞争性结合 miR-21-5p 上调 TIMP3 的表达。过表达的 HAND2-AS1 或下调的 miR-21-5p 抑制细胞增殖、迁移和侵袭，同时促进细胞凋亡，这与 VEGFA 信号通路中蛋白质的表达增加有关。这些变化被 TIMP3 的沉默所逆转。过表达的 HAND2-AS1 降低了裸鼠的肿瘤形成能力。总之，HAND2-AS1 可能通过其对 miR-21-5p/TIMP3/VEGFA 轴的调节对宫颈癌细胞生长和宫颈癌发展发挥抑制作用。这凸显了 HAND2-AS1 可能作为宫颈癌诊断和治疗的潜在靶点。