Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer. Mol Cancer 2019 11 29;18(1):171
Date
11/30/2019Pubmed ID
31779616Pubmed Central ID
PMC6883523DOI
10.1186/s12943-019-1107-yScopus ID
2-s2.0-85075794753 40 CitationsAbstract
INTRODUCTION: Long noncoding RNAs (lncRNAs) are emerging as key players in the development and progression of cancer. However, the biological role and clinical significance of most lncRNAs in lung carcinogenesis remain unclear. In this study, we identified and explored the role of a novel lncRNA, lung cancer associated transcript 1 (LCAT1), in lung cancer.
METHODS: We predicted and validated LCAT1 from RNA-sequencing (RNA-seq) data of lung cancer tissues. The LCAT1-miR-4715-5p-RAC1 axis was assessed by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Signaling pathways altered by LCAT1 knockdown were identified using RNA-seq. Furthermore, the mechanism of LCAT1 was investigated using loss-of-function and gain-of-function assays in vivo and in vitro.
RESULTS: LCAT1 is an oncogene that is significantly upregulated in lung cancer tissues and associated with poor prognosis. LCAT1 knockdown caused growth arrest and cell invasion in lung cancer cells in vitro, and inhibited tumorigenesis and metastasis in the mouse xenografts. Mechanistically, LCAT1 functions as a competing endogenous RNA for miR-4715-5p, thereby leading to the upregulation of the activity of its endogenous target, Rac family small GTPase 1 (RAC1). Moreover, EHop-016, a small molecule inhibitor of RAC1, as an adjuvant could improve the Taxol monotherapy against lung cancer cells in vitro.
CONCLUSIONS: LCAT1-miR-4715-5p-RAC1/PAK1 axis plays an important role in the progression of lung cancer. Our findings may provide valuable drug targets for treating lung cancer. The novel combination therapy of Taxol and EHop-016 for lung cancer warrants further investigation, especially in lung cancer patients with high LCAT1 expression.
Author List
Yang J, Qiu Q, Qian X, Yi J, Jiao Y, Yu M, Li X, Li J, Mi C, Zhang J, Lu B, Chen E, Liu P, Lu YAuthor
Pengyuan Liu PhD Adjunct Professor in the Physiology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Gene Silencing
Humans
Kaplan-Meier Estimate
Lung Neoplasms
Mice
MicroRNAs
Models, Biological
Neoplasm Metastasis
Oncogenes
Paclitaxel
Prognosis
RNA Interference
RNA, Long Noncoding
rac1 GTP-Binding Protein
