RGD Reference Report - Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer. - Rat Genome Database

RGD Reference Report - Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer. - Rat Genome Database

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Long noncoding RNA LCAT1 functions as a ceRNA to regulate RAC1 function by sponging miR-4715-5p in lung cancer.
Authors:	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
Citation:	Yang J, etal., Mol Cancer. 2019 Nov 29;18(1):171. doi: 10.1186/s12943-019-1107-y.
RGD ID:	152998910
Pubmed:	PMID:31779616 (View Abstract at PubMed)
PMCID:	PMC6883523 (View Article at PubMed Central)
DOI:	DOI:10.1186/s12943-019-1107-y (Journal Full-text)
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.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
lung adenocarcinoma	exacerbates	HEP		152998910	mRNA:increased expression:lung (human)	RGD

Objects Annotated

Genes (Homo sapiens)

RAC1 (Rac family small GTPase 1)

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