长链非编码RNA通过调控-PAK1途径促进舌鳞状细胞癌的进展。（注：原文中“-PAK1”表述有误，推测可能是“PAK1”，若按此正确表述翻译为“长链非编码RNA通过调控PAK1途径促进舌鳞状细胞癌的进展” ）

lncRNA potentiates the progression of tongue squamous cell carcinoma through regulating -PAK1 pathway.

作者信息

Zhu Minhui, Zhang Caiyun, Chen Donghui, Chen Shicai, Zheng Hongliang

机构信息

Department of Otorhinolaryngology- Head and Neck Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China,

出版信息

Onco Targets Ther. 2019 Feb 19;12:1365-1377. doi: 10.2147/OTT.S192069. eCollection 2019.

DOI:10.2147/OTT.S192069

PMID:30863103

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6388959/

Abstract

BACKGROUND

Tongue squamous cell carcinoma (TSCC) is the second most common malignancy in oral carcinoma. lncRNA metastasis-associated lung adenocarcinoma transcript 1 () was regarded as an oncogenic factor in various carcinomas. However, its underlying molecular mechanisms in the development and progression of TSCC have not been well featured till now.

METHODS

The expressions of , and p21 (RAC1)-activated kinase 1 (PAK1) mRNA were measured by RT-qPCR assay. The protein level of PAK1 was determined by western blot analysis. Cell viability was detected by Cell Counting Kit-8 assay. Transwell chamber was used to detect cell migratory and invasive capability. Luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and biotin pull-down assay were applied to evaluate the relationship between , and PAK1. Xenograft experiments were performed to assess the effect and mechanism of in TSCC tumor growth.

RESULTS

The expression of and p21 (RAC1)-activated kinase 1 (PAK1) was upregulated and microRNA-140-5p () expression was downregulated in TSCC tissues and cells. knockdown induced expression by direct interaction. Moreover, knockdown inhibited proliferation, migration, and invasion by upregulating expression in TSCC cells. Additionally, PAK1 was identified as a direct target of . Also, knockdown inhibited PAK1 expression by upregulating in TSCC cells. Furthermore, overexpression curbed the proliferation, migration, and invasion of TSCC cells by targeting PAK1. Finally, knockdown inhibited tumor growth by upregulating and downregulating PAK1 in mouse xenograft models of TSCC.

CONCLUSION

contributed to TSCC progression via -PAK1 regulatory axis, highlighting a potential target for TSCC management.

摘要

背景

舌鳞状细胞癌（TSCC）是口腔癌中第二常见的恶性肿瘤。长链非编码RNA转移相关肺腺癌转录本1（）在多种癌症中被视为致癌因子。然而，其在TSCC发生发展中的潜在分子机制至今尚未完全明确。

方法

采用逆转录定量聚合酶链反应（RT-qPCR）检测、和p21（RAC1）激活激酶1（PAK1）mRNA的表达。通过蛋白质免疫印迹分析测定PAK1的蛋白水平。采用细胞计数试剂盒-8法检测细胞活力。利用Transwell小室检测细胞迁移和侵袭能力。应用荧光素酶报告基因检测、RNA结合蛋白免疫沉淀（RIP）检测和生物素下拉检测评估、与PAK1之间的关系。进行异种移植实验以评估在TSCC肿瘤生长中的作用及机制。

结果

在TSCC组织和细胞中，和p21（RAC1）激活激酶1（PAK1）的表达上调，而微小RNA-140-5p（）的表达下调。敲低通过直接相互作用诱导表达。此外，敲低通过上调TSCC细胞中的表达来抑制增殖、迁移和侵袭。另外，PAK1被确定为的直接靶点。而且，敲低通过上调TSCC细胞中的表达来抑制PAK1表达。此外，过表达通过靶向PAK1抑制TSCC细胞的增殖、迁移和侵袭。最后，在TSCC小鼠异种移植模型中，敲低通过上调和下调PAK1来抑制肿瘤生长。