Department of Gynecology, Zhoukou Central Hospital, Zhoukou City, Henan Province, 466000, PR. China.
Department of Gynecology, Zhoukou Central Hospital, Zhoukou City, Henan Province, 466000, PR. China
Biosci Rep. 2018 Nov 13;38(6). doi: 10.1042/BSR20181213. Print 2018 Dec 21.
Long non-coding RNAs (lncRNAs) snaR is a newly identified lncRNA with known functionality only in colon cancer. Our study was carried out to investigate the involvement of lncRNA snaR in human papillomaviruses (HPV)-negative cervical squamous cell carcinoma (CSCC). In the present study, plasma levels of lncRNA snaR in 108 patients with HPV-negative CSCC at stage I and II, and 35 healthy female controls were detected by real-time quantitative PCR. ROC curve analysis was performed to evaluate the diagnostic value of lncRNA snaR for HPV-negative CSCC. All patients were subjected to surgical resection and followed-up for 5 years to record cancer recurrence. lncRNA snaR expression vectors were transfected into HPV-negative CSCC cells. Cell migration and invasion ability were evaluated by Transwell migration and invasion assay, respectively. Expression levels of TGF-β1 were determined by Western blot. It was observed that lncRNA snaR was down-regulated in HPV-negative CSCC patients comparing with healthy controls. Down-regulation of lncRNA snaR effectively distinguished HPV-negative CSCC patients from healthy controls. lncRNA snaR was further down-regulated in patients with distant recurrence (DR) but not in patients with local-recurrence or without recurrence. lncRNA snaR overexpression decreased TGF-β1 expression in CSCC cells, while exogenous TGF-β1 treatment showed no significant effects on lncRNA snaR expression. lncRNA snaR overexpression inhibited cancer cell migration and invasion, while TGF-β1 treatment attenuated the inhibitory effect of lncRNA snaR overexpression on cancer cell migration and invasion. We therefore conclude that down-regulation of lncRNA snaR may induce postoperative DR of HPV-negative CSCC possibly through the interactions with TGF-β1.
长链非编码 RNA（lncRNA）snaR 是一种新鉴定的 lncRNA，仅在结肠癌中具有已知功能。我们的研究旨在探讨 lncRNA snaR 在人乳头瘤病毒（HPV）阴性宫颈鳞状细胞癌（CSCC）中的作用。本研究采用实时定量 PCR 检测 108 例 I 期和 II 期 HPV 阴性 CSCC 患者和 35 例健康女性对照者血浆 lncRNA snaR 水平，采用 ROC 曲线分析评估 lncRNA snaR 对 HPV 阴性 CSCC 的诊断价值。所有患者均行手术切除，并随访 5 年记录癌症复发情况。将 lncRNA snaR 表达载体转染至 HPV 阴性 CSCC 细胞，采用 Transwell 迁移和侵袭实验分别评估细胞迁移和侵袭能力，采用 Western blot 检测 TGF-β1 表达水平。结果发现，与健康对照组相比，HPV 阴性 CSCC 患者 lncRNA snaR 表达下调。下调 lncRNA snaR 可有效区分 HPV 阴性 CSCC 患者与健康对照组。lncRNA snaR 在远处复发（DR）患者中进一步下调，但在局部复发或无复发患者中未下调。lncRNA snaR 过表达降低了 CSCC 细胞中 TGF-β1 的表达，而外源性 TGF-β1 处理对 lncRNA snaR 表达无显著影响。lncRNA snaR 过表达抑制了癌细胞的迁移和侵袭，而 TGF-β1 处理减弱了 lncRNA snaR 过表达对癌细胞迁移和侵袭的抑制作用。因此，我们得出结论，lncRNA snaR 的下调可能通过与 TGF-β1 的相互作用诱导 HPV 阴性 CSCC 术后 DR。
