长链非编码RNA TTN-AS1通过miR-411-3p/NFAT5轴促进口腔鳞状细胞癌的进展。

LncRNA TTN-AS1 promotes the progression of oral squamous cell carcinoma via miR-411-3p/NFAT5 axis.

作者信息

Fu Su-Wei, Zhang Yan, Li Shen, Shi Zhi-Yan, Zhao Juan, He Qing-Li

机构信息

Department of Stomatology, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No.7 Weiwu Road, Zhengzhou, 450003 Henan China.

出版信息

Cancer Cell Int. 2020 Aug 28;20:415. doi: 10.1186/s12935-020-01378-6. eCollection 2020.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is a common kind of squamous cell carcinoma of the head and neck, which is a threat to public health. Long noncoding RNAs (lncRNAs) are associated with the development of various diseases, including cancers. LncRNA titin antisense RNA 1 (TTN-AS1) is known as a crucial regulatory factor in several cancers. Nevertheless, the specific functions of TTN-AS1 in OSCC remains obscure.

METHODS

The expression of TTN-AS1 in OSCC samples or cells was analyzed through qRT-PCR. Colony formation assay, EdU assay, flow cytometry assay, TUNEL assay and wound healing assay were conducted to estimate the functions of TTN-AS1 in OSCC cells. RIP and luciferase reporter assays were utilized to detect the interaction between TTN-AS1 and miR-411-3p as well as between miR-411-3p and NFAT5.

RESULTS

TTN-AS1 expression was stronger in OSCC cells. Knockdown of TTN-AS1 effectively restrained cell proliferation and migration but had inductive role in apoptosis. Moreover, TTN-AS1 could function as the miR-411-3p sponge in OSCC and miR-411-3p exerted the inhibitory functions on OSCC cell growth. In addition, NFAT5 was proven as the target of miR-411-3p. Rescue assay indicated that overexpressing NFAT5 could reverse the inhibitory function of TTN-AS1 depletion on cell growth.

CONCLUSION

lncRNA TTN-AS1 contributed to the progression of OSCC via miR-411-3p/NFAT5 axis.

背景

口腔鳞状细胞癌（OSCC）是头颈部常见的鳞状细胞癌类型，对公众健康构成威胁。长链非编码RNA（lncRNAs）与包括癌症在内的多种疾病的发生发展相关。lncRNA肌联蛋白反义RNA 1（TTN-AS1）在多种癌症中被认为是关键调控因子。然而，TTN-AS1在OSCC中的具体功能仍不清楚。

方法

通过qRT-PCR分析OSCC样本或细胞中TTN-AS1的表达。进行集落形成试验、EdU试验、流式细胞术试验、TUNEL试验和伤口愈合试验以评估TTN-AS1在OSCC细胞中的功能。利用RIP和荧光素酶报告基因试验检测TTN-AS1与miR-411-3p之间以及miR-411-3p与NFAT5之间的相互作用。

结果

TTN-AS1在OSCC细胞中表达较强。敲低TTN-AS1可有效抑制细胞增殖和迁移，但对细胞凋亡有诱导作用。此外，TTN-AS1在OSCC中可作为miR-411-3p的海绵，miR-411-3p对OSCC细胞生长发挥抑制作用。另外，NFAT5被证明是miR-411-3p的靶标。挽救试验表明，过表达NFAT5可逆转TTN-AS1缺失对细胞生长的抑制作用。