Department of Gynecology, The First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Department of Gynecology, The Cancer Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
J Cell Biochem. 2021 Feb;122(2):235-248. doi: 10.1002/jcb.29846. Epub 2020 Sep 22.
Long noncoding RNAs (lncRNAs) have drawn growing attention due to their regulatory roles in various diseases, including tumors. Recently, lncRNA FOXD3 antisense RNA 1 (FOXD3-AS1) was shown to be overexpressed in colon adenocarcinoma and glioma, exerting oncogenic functions. However, its expression and effects in cervical cancer (CC) remained unknown. In this research, our group first reported that the levels of FOXD3-AS1 were distinctly elevated in CC samples and cell lines. The distinct upregulation of FOXD3-AS1 was associated with lymphatic invasion, distant metastasis, and International Federation of Gynecology and Obstetrics stage, and also predicted poor clinical results of CC patients. Next, transcription factor SP1 was demonstrated to resulting in the upregulation of FOXD3-AS1 in CC. Functional assays indicated that knockdown of FOXD3-AS1 distinctly suppressed CC progression via affecting cell proliferation, cell apoptosis, and metastasis. Moreover, mechanistic studies suggested that FOXD3-AS1 acted as an endogenous sponge by directly binding miR-296-5p, resulting in the suppression of miR-296-5p. In addition, we also reported that high mobility group A, a direct target of miR-296-5p, could mediate the tumor-promotive effects that FOXD3-AS1 displayed. Overall, our present study might help to lead a better understanding of the pathogenesis of CC, provide a novel possible tumor biomarker, and probe the feasibility of lncRNA-directed treatments for CC.
长链非编码 RNA（lncRNAs）因其在包括肿瘤在内的各种疾病中的调节作用而受到越来越多的关注。最近，lncRNA FOXD3 反义 RNA1（FOXD3-AS1）在结肠腺癌和神经胶质瘤中被证明过度表达，发挥致癌作用。然而，其在宫颈癌（CC）中的表达和作用尚不清楚。在这项研究中，我们小组首次报道 FOXD3-AS1 在 CC 样本和细胞系中的水平明显升高。FOXD3-AS1 的明显上调与淋巴侵袭、远处转移和国际妇产科联合会（FIGO）分期有关，并且还预测了 CC 患者的不良临床结果。接下来，转录因子 SP1 被证明导致 CC 中 FOXD3-AS1 的上调。功能测定表明，FOXD3-AS1 的敲低通过影响细胞增殖、细胞凋亡和转移明显抑制 CC 的进展。此外，机制研究表明，FOXD3-AS1 作为内源性海绵通过直接结合 miR-296-5p，从而抑制 miR-296-5p。此外，我们还报道了高迁移率族蛋白 A，miR-296-5p 的直接靶标，可介导 FOXD3-AS1 显示的促肿瘤作用。总的来说，本研究可能有助于更好地理解 CC 的发病机制，提供一种新的潜在肿瘤标志物，并探讨基于 lncRNA 的治疗 CC 的可行性。
