Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer

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, lun...

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Vydáno v:	Molecular cancer Ročník 18; číslo 1; s. 171 - 16
Hlavní autoři:	Yang, Juze, Qiu, Qiongzi, Qian, Xinyi, Yi, Jiani, Jiao, Yiling, Yu, Mengqian, Li, Xufan, Li, Jia, Mi, Chunyi, Zhang, Jisong, Lu, Bingjian, Chen, Enguo, Liu, Pengyuan, Lu, Yan
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London BioMed Central 29.11.2019 BioMed Central Ltd Springer Nature B.V BMC
Témata:	Antisense RNA Biomarkers Biomedical and Life Sciences Biomedicine Cancer cells Cancer metastasis Cancer Research Carcinogenesis Cell cycle Cell growth Development and progression Flow cytometry Gene expression Guanosine triphosphatases Immunoprecipitation Laboratory animals Long noncoding RNAs Luciferase Lung cancer Medical prognosis Metastases Metastasis miR-4715-5p Novels Oncogene Oncology Paclitaxel Pathogenesis RAC1 Rac1 protein Ribonucleic acid RNA Transcription Tumorigenesis Tumors Xenografts Massachusetts China United States > US Japan miR-4715-5p RAC1 Lung cancer Oncogene Long noncoding RNAs
ISSN:	1476-4598, 1476-4598
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1476-4598 1476-4598
DOI:	10.1186/s12943-019-1107-y