CCAT1/FABP5 promotes tumour progression through mediating fatty acid metabolism and stabilizing PI3K/AKT/mTOR signalling in lung adenocarcinoma

Abstract

Lung adenocarcinoma (LUAD) is the commonest subtype of non-small cell lung cancer (NSCLC). 1,2 Despite significant progress achieved in clinical and experimental ontology, the prognosis of LUAD still presents a gloomy prospective. 3,4 Early diagnosis is important for the successful treatment of LUAD, and however, patients with LUAD usually are diagnosed at advanced stage or with metastasis. 5 Therefore, the identification of novel diagnosis and therapeutic biomarkers for LUAD patients is in great urgency.Over the past decade, with development of whole-genome sequencing technology, particular attention has been paid on the exploding class of transcripts of long non-coding RNAs (lncRNAs), arbitrarily defined according to a length over 200 nucleotides. 6,7 Once considered as transcriptional noise, lncRNAs are now revealed by steadily growing lists to play authentic biological roles. Many lncRNAs are identified to share common characteristics

Metastatic Tumor Cell-Specific FABP7 Promotes NSCLC Metastasis via Inhibiting β-Catenin Degradation

“…The scRNA-seq results show that only FABP3/4/5/7, and a very small amount of FABP6, are expressed in NSCLC. In this malignancy, FABP5 was reported to facilitate tumorigenesis and metastasis [ 52 , 53 ], while the functions of FABP3 and 4 are less clear and even become controversial [ 54 ], and the role of FABP6 and 7 remain unclarified in NSCLC. In fact, our work firstly reports the pro-metastatic function of FABP7 in NSCLC.…”

Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression

“… 92 , 93 Activated AKT regulates cell proliferation, differentiation, migration, and apoptosis by activating or inhibiting downstream target proteins, such as Bad, 94 Caspase9, 95 NF-κB, 96 , 97 GSK-3, 98 FKHR, 99 , 100 p21, 101 p53 102 and FOXO1. 103 , 104 Aberrant activation of PI3K/AKT pathway has been found in a variety of cancers, 105 such as lung cancer, 106 esophageal cancer, 107 gastric cancer, 108 breast cancer, 109 laryngeal cancer, 110 gallbladder cancer, 111 and prostate cancer. 112 …”

Long Noncoding RNAs and Circular RNAs in the Metabolic Reprogramming of Lung Cancer: Functions, Mechanisms, and Clinical Potential

“…Importantly, this FABP-5/PPAR- δ signaling pathway may contribute to tumor progression [ 107 – 110 ]. Chen et al reported that lncRNA colon cancer-associated transcript 1 (CCAT1), which is remarkably upregulated in lung adenocarcinoma tissues and cell lines, promotes proliferation and angiogenesis in vitro and facilitates carcinogenesis and metastasis in vivo [ 50 ]. Functionally, CCAT1 promotes the reprogramming of fatty acid metabolism, as shown by increased lipid accumulation in lung adenocarcinoma cell lines and enhanced expression of several key fatty acid enzymes such as FAS, ACC1, and acyl-CoA oxidase 1.…”

“…The circRNAs comprise circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-ERBB2, circTADA2A, circ-PGC, circPUM1, circ_0000517, circ-PITX1, circ_0006677, circNFIX, circ-ENO1, circ-LDLRAD3, and circ_0003028 [ 20 , 24 , 29 , 30 , 32 , 39 – 48 , 52 , 55 ]. In fact, some of them were also shown to have potential as prognostic indicators in patients with LC; they included DUXAP8, LINC00243, AC020978, LINC01123, HOXA11-AS, ABHD11-AS1, AL355338, circMYLK, circMAGI3, circAGFG1, circSLC25A16, circ-MEMO1, circDCUN1D4, circ-PGC, circPUM1, circ_0000517, circ_0006677, circNFIX, CCAT1, and MINCR [ 20 , 22 , 24 , 26 , 29 – 36 , 39 , 42 – 44 , 46 , 47 , 50 , 53 ]. Besides, two other lncRNAs, LINC01537 and ARHGAP10, were only found to have potential as prognostic indicators [ 19 , 38 ].…”

“…Clinically, the expression of IGFBP4-1, ABHD11-AS1, circMAGI3, circSLC25A16, circDCUN1D4, and circPUM1 in LC tissues was associated with TNM stage; the expression of DUXAP8, circ_0000517, and circ-LDLRAD3 correlated with TNM stage and LNM; while the expression of AC020978, HOXA11-AS, circ-PGC, and circ_0006677 was associated with TNM stage, LNM, and tumor size [ 22 – 24 , 26 , 30 , 33 , 35 , 39 , 42 – 44 , 46 , 52 ]. In addition, CRYBG3 expression correlated with distant metastasis; CCAT1 expression correlated with clinical stage; circNFIX expression was associated with TNM stage and distant metastasis; circ-MEMO1 expression correlated with clinical stage and LNM; circMYLK was associated with TNM stage and tumor size; LINC01123 expression was associated with TNM stage, T stage, and LNM, while AL355338 expression was associated with TNM stage, T stage, LNM, and distant metastasis [ 20 , 28 , 31 , 32 , 36 , 47 , 50 ].…”