长链非编码 RNA UCA1 通过靶向口腔鳞状细胞癌中的 miR-143-3p 促进细胞生长、迁移和侵袭。

Long noncoding RNA UCA1 promotes cell growth, migration, and invasion by targeting miR-143-3p in oral squamous cell carcinoma.

机构信息

Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Oral and Maxillofacial Surgery, Affiliated Hangzhou First People's Hospital, Medical College of Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

Cancer Med. 2020 May;9(9):3115-3129. doi: 10.1002/cam4.2808. Epub 2020 Mar 4.

BACKGROUND

The long noncoding RNA (lncRNA) urothelial carcinoma-associated 1 (UCA1) is dysregulated in many types of tumors; however, its role in oral squamous cell carcinoma (OSCC) remains unclear. This study aims to determine the effect of lncRNA UCA1 on OSCC.

METHODS

Fifty-six paired OSCC and adjacent nontumorous tissues were collected and the levels of UCA1, miR-143-3p, and MYO6 in the tissues were evaluated by qRT-PCR. In in vitro experiments, cell viability, migration, and invasion were measured by, respectively, performing CCK-8, wound healing, and transwell assays. The target relationships among UCA1, miR-143-3p, and MYO6 were verified by dual-luciferase assay. Western blot and immunohistochemistry were carried out to determine the protein levels. Xenograft mouse model was established to explore the effects of UCA1 in vivo.

RESULTS

Levels of UCA1 and MYO6 were increased significantly in OSCC, while the level of miR-143-3p was decreased compared with the adjacent nontumorous tissues. UCA1 promoted OSCC cell growth, migration, and invasion both in vitro and in vivo, while miR-143-3p reversed the progression. MYO6 was validated as a target for miR-143-3p, and MYO6 overexpression reversed the effects of miR-143-3p mimic on OSCC cells.

CONCLUSION

LncRNA UCA1 contributes to the proliferation and metastasis of OSCC cells by targeting miR-143-3p and upregulating its downstream gene MYO6. UCA1 could serve as a promising novel target therapy for treatment of OSCC.

背景

长链非编码 RNA (lncRNA) 尿路上皮癌相关 1 (UCA1) 在多种肿瘤中失调；然而，其在口腔鳞状细胞癌 (OSCC) 中的作用尚不清楚。本研究旨在确定 lncRNA UCA1 对 OSCC 的影响。

方法

收集 56 对 OSCC 和相邻非肿瘤组织，通过 qRT-PCR 评估组织中 UCA1、miR-143-3p 和 MYO6 的水平。在体外实验中，通过 CCK-8、划痕愈合和 Transwell 实验分别测量细胞活力、迁移和侵袭。通过双荧光素酶报告实验验证 UCA1、miR-143-3p 和 MYO6 之间的靶关系。通过 Western blot 和免疫组化检测蛋白水平。建立异种移植小鼠模型以体内研究 UCA1 的作用。

结果

与相邻非肿瘤组织相比，OSCC 中 UCA1 和 MYO6 的水平显著升高，而 miR-143-3p 的水平降低。UCA1 促进 OSCC 细胞在体外和体内的生长、迁移和侵袭，而 miR-143-3p 逆转了进展。MYO6 被验证为 miR-143-3p 的靶基因，MYO6 的过表达逆转了 miR-143-3p 模拟物对 OSCC 细胞的影响。