Acta Biochim Biophys Sin (Shanghai). 2022 Mar 25;54(3):321-331. doi: 10.3724/abbs.2022016.
Emerging evidence has proved the essential roles of long non-coding RNAs (lncRNAs) in cervical carcinoma (CC). LncRNA lung adenocarcinoma-associated transcript 1 (LUADT1) is overexpressed and plays an oncogenic role in various cancers; however, the function and clinical values of LUADT1 in CC remain unclear. In this study we found that LUADT1 is highly expressed in CC tissues and cells. Up-regulated LUADT1 is significantly correlated with the more aggressive status and poorer survival of CC patients. studies show that LUADT1 depletion suppresses CC proliferation, and leads to cell apoptosis and cell cycle arrest. Furthermore, the xenograft mouse assay demonstrates that LUADT1 knockdown remarkably suppresses tumor growth. Mechanistically, LUADT1 binds to miR-1207-5p and inhibits miR-1207-5p expression in CC cells. Septin 9 (SEPT9) is identified as a miR-1207-5p target which is negatively regulated by LUADT1. Overexpression of SEPT9 abrogates the suppressed proliferation of CC cells induced by LUADT1 knockdown. These results demonstrate that LUADT1 sponges miR-1207-5p and consequently modulates SEPT9 expression in CC. Our study suggests the possible application of LUADT1 as a prognostic and therapeutic target to inhibit CC.
越来越多的证据证明长非编码 RNA（lncRNA）在宫颈癌（CC）中起着重要作用。长非编码 RNA 肺腺癌相关转录本 1（LUADT1）在多种癌症中表达上调并发挥致癌作用；然而，LUADT1 在 CC 中的功能和临床价值仍不清楚。在本研究中，我们发现 LUADT1 在 CC 组织和细胞中高表达。上调的 LUADT1 与 CC 患者更具侵袭性的状态和更差的生存显著相关。研究表明，LUADT1 耗竭抑制 CC 增殖，并导致细胞凋亡和细胞周期停滞。此外，异种移植小鼠实验表明，LUADT1 敲低显著抑制肿瘤生长。机制上，LUADT1 与 miR-1207-5p 结合并抑制 CC 细胞中 miR-1207-5p 的表达。Septin 9（SEPT9）被鉴定为 miR-1207-5p 的靶基因，其受 LUADT1 负调控。SEPT9 的过表达可消除 LUADT1 敲低诱导的 CC 细胞增殖抑制。这些结果表明，LUADT1 作为 CC 中的一个预后和治疗靶点，可能通过海绵吸附 miR-1207-5p 来调节 SEPT9 的表达。我们的研究表明，LUADT1 可能作为一种抑制 CC 的预后和治疗靶点。
