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长链非编码 RNA ST7-AS1 通过稳定 CARM1 促进喉鳞状细胞癌。

The long noncoding RNA ST7-AS1 promotes laryngeal squamous cell carcinoma by stabilizing CARM1.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China.

Department of Otolaryngology, Head and Neck Surgery, Liaocheng People's Hospital, Liaocheng, 252000, Shandong, China.

出版信息

Biochem Biophys Res Commun. 2019 Apr 23;512(1):34-40. doi: 10.1016/j.bbrc.2019.02.057. Epub 2019 Mar 7.

DOI:10.1016/j.bbrc.2019.02.057
PMID:30853182
Abstract

The laryngeal squamous cell carcinoma (LSCC) represents a malignant cancer and contributes largely to head and neck tumorigenesis. The molecular mechanisms for LSCC progression are poorly understood. In current work, we identified long non-coding RNA (lncRNA) termed suppressor of tumorigenicity 7 antisense RNA 1 (ST7-AS1) as an oncogenic factor in LSCC. ST7-AS1 is frequently overexpressed in LSCC tissues and cell lines. ST7-AS1 is required for the malignancy of LSCC cells through migration, tumor sphere formation assay and in vivo implantation. Mechanistically, ST7-AS1 could interact with CARM1, a well characterized protein arginine methyltransferase and protect CARM1 from ubiquitin-dependent degradation. CARM1 can methylate Sox-2, a pluripotent transcription factor. Thus, ST7-AS1 might mediate its oncogenic effect by signaling through CARM1-Sox-2 axis to enhance Sox-2 self-association and transactivation activity. Collectively, we have unraveled a ST7-AS1/CARM1/Sox-2 signaling axis in LSCC and may have created novel interconnections between noncoding RNAs and cancer development.

摘要

喉鳞状细胞癌(LSCC)是一种恶性肿瘤,是头颈部肿瘤发生的主要原因。LSCC 进展的分子机制尚不清楚。在目前的工作中,我们发现长非编码 RNA(lncRNA)称为抑瘤性 7 反义 RNA 1(ST7-AS1)是 LSCC 中的致癌因子。ST7-AS1 在 LSCC 组织和细胞系中经常过表达。ST7-AS1 通过迁移、肿瘤球形成试验和体内植入对 LSCC 细胞的恶性表型是必需的。从机制上讲,ST7-AS1 可以与 CARM1 相互作用,CARM1 是一种特征明确的蛋白质精氨酸甲基转移酶,可以保护 CARM1 免受泛素依赖性降解。CARM1 可以甲基化多能转录因子 Sox-2。因此,ST7-AS1 可能通过 CARM1-Sox-2 轴信号转导来介导其致癌作用,从而增强 Sox-2 自我缔合和反式激活活性。综上所述,我们已经揭示了 LSCC 中的 ST7-AS1/CARM1/Sox-2 信号轴,并可能在非编码 RNA 和癌症发展之间建立了新的联系。

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