Department of Otolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Otolaryngology, XuZhou Central Hospital, XuZhou Clinical School of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Bull Exp Biol Med. 2023 Sep;175(5):673-680. doi: 10.1007/s10517-023-05924-w. Epub 2023 Oct 24.
This study aimed to explore the biological role and mechanism underlying the effects of colon cancer-associated transcript 2 (CCAT2), a long noncoding RNA (lncRNA) in human laryngeal squamous cell carcinoma (LSCC). CCAT2 expression levels in clinical LSCC samples and TU-212 cell line were evaluated by quantitative real-time PCR. The correlation of CCAT2 expression level with clinical-pathological characteristics of patients and their prognosis was analyzed. The functional role of CCAT2 in human LSCC was assessed by Cell Counting Kit-8, Transwell assay, flow cytometric analysis, and LSCC xenograft experiment in vivo. The expression of potential targeted proteins was detected by Western blotting and immunohistochemistry. We found that expression of CCAT2 was significantly elevated in LSCC tissues and TU-212 cells (p<0.05). Survival analysis showed that LSCC patients with high expression of CCAT2 had a shorter 5-year overall survival rate than those with low expression (p<0.05). In addition, CCAT2 silencing with short hairpin RNA significantly decreased the proliferative and invasive potential of TU-212 cells (p<0.05) and promoted their apoptosis. In Nude mice, CCAT2 knockdown suppressed the growth of tumor and decreased its volume and weight in comparison with the controls (p<0.05). In TU-212 cells, CCAT2 silencing with short hairpin RNA significantly down-regulated the expression of β-catenin and CDK8 (p<0.05). Thus, knockdown of CCAT2 suppresses proliferation and invasion of the cells and inhibits Wnt/β-catenin signaling pathway in LSCC, which indicates novel therapeutic targets and prognostic indicators in patients with LSCC.
本研究旨在探讨结肠癌相关转录物 2（CCAT2）在人喉鳞状细胞癌（LSCC）中的生物学作用和机制，CCAT2 是一种长链非编码 RNA（lncRNA）。通过实时定量 PCR 评估临床 LSCC 样本和 TU-212 细胞系中 CCAT2 的表达水平。分析 CCAT2 表达水平与患者临床病理特征及其预后的相关性。通过细胞计数试剂盒-8、Transwell 测定、流式细胞术分析和体内 LSCC 异种移植实验评估 CCAT2 在人 LSCC 中的功能作用。通过 Western blot 和免疫组化检测潜在靶向蛋白的表达。我们发现 CCAT2 在 LSCC 组织和 TU-212 细胞中的表达明显升高（p<0.05）。生存分析显示，CCAT2 高表达的 LSCC 患者的 5 年总生存率低于低表达的患者（p<0.05）。此外，短发夹 RNA 沉默 CCAT2 显著降低了 TU-212 细胞的增殖和侵袭潜力（p<0.05）并促进其凋亡。在裸鼠中，与对照组相比，CCAT2 敲低抑制了肿瘤的生长并降低了其体积和重量（p<0.05）。在 TU-212 细胞中，短发夹 RNA 沉默 CCAT2 显著下调了 β-连环蛋白和 CDK8 的表达（p<0.05）。因此，CCAT2 的敲低抑制了 LSCC 细胞的增殖和侵袭，并抑制了 Wnt/β-连环蛋白信号通路，这表明 LSCC 患者的新的治疗靶点和预后指标。
