Long Noncoding RNA LINC01554 Inhibits the Progression of NSCLC Progression by Functioning as a ceRNA for miR-1267 and Regulating ING3/Akt/mTOR Pathway

Abstract

Objectives. This study focused on the biological functions and mechanisms of action of LINC01554 in nonsmall cell lung cancer (NSCLC). Methods. The expression and prognostic values of LINC01554 in NSCLC were evaluated using The Cancer Genome Atlas datasets. MTT, colony formation, wound healing, transwell, and in vivo assays were performed to investigate the role of LINC01554 in NSCLC. The related protein expression levels were measured via western blotting. Bioinformatic analysis was conducted to predict targeted genes. The relationship between LINC01554, microRNA- (miR-) 1267, miR-1267, and inhibitor of growth family member 3 (ING3) was analysed via a dual-luciferase reporter assay. Results. LINC01554 expression was downregulated in NSCLC and associated with NSCLC prognosis. LINC01554 overexpression suppressed NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Bioinformatic and dual-luciferase reporter assays demonstrated that LINC01554 expression directly targeted miR-1267 expression, which in turn directly acted on ING3. An miR-1267 mimic significantly reduced ING3 expression, whereas an miR-1267 inhibitor observably elevated its expression. LINC01554 overexpression increased ING3 expression, whereas this effect was counteracted by the miR-1267 mimic. LINC01554 overexpression also significantly suppressed the expression of phosphorylated protein kinase B (Akt) and phosphorylated mammalian target of rapamycin (mTOR) expression; this effect was abrogated by the miR-1267 mimic. Mechanistically, LINC01554 overexpression repressed the growth, migration, invasion, and epithelial-mesenchymal transition (EMT) of NSCLC cells through the regulation of the miR-1267/ING3 axis via regulation of the Akt/mTOR signalling pathway. Conclusions. We provide the first evidence of the involvement of the LINC01554/miR-1267 axis in NSCLC proliferation and metastasis through the ING3Akt/mTOR pathway. Thus, LINC01554 may serve as a novel therapeutic target for NSCLC.

Long non-coding RNA LINC01554 overexpression suppresses viability, migration, and invasion of liver cancer cells through regulating miR-148b-3p/EIF4E3

“…After searching the literatures, the roles of lncRNA HAND2-AS1 in liver cancer have been fully reported previously ([ 11 , 18 ]), while no studies have reported the specific roles of lncRNA RP11-557H15.4 in human diseases. Additionally, for lncRNA LINC01554, some studies have reported its roles in other cancers, such as NSCLC [ 19 ], laryngeal squamous cell carcinoma [ 20 ], and esophageal squamous cell carcinoma [ 21 ], but its action mechanisms in HCC are still unclear. Additionally, it was also found that compared with the paracancerous tissues, the level of LINC01554 was significantly decreased in the cancer tissues ( P < 0.05, Fig.…”

miRNAs as Interconnectors between Obesity and Cancer

“…In lung carcinomas, differential expression of lncRNAs has been observed depending on the cancer type. Representative cases are SLC9A3-AS1, reported upregulated; LINC01554 and GABPB1 reported downregulated in NSCLC tissues [166][167][168], while RBPMS-AS1 expression was found to be diminished in lung adenocarcinoma [169]. Other studies have shown the reduced expression of LINC00294 in colorectal carcinoma tissues [170], while SLFNL1-AS1, KCNQ1OT1, NEAT1, XIST, AC016876.2, AC026362.1 were found to be downregulated in colon cancer cell lines [171].…”

Using ncRNAs as Tools in Cancer Diagnosis and Treatment—The Way towards Personalized Medicine to Improve Patients’ Health

“…In several types of cancer, most lncRNAs are either up- or downregulated. These lncRNAs favor all stages of tumor development through the promotion of mRNA expression and constancy [ 253 ], by favoring mRNA stability [ 254 ], or by modulating miR [ 254 , 255 , 256 , 257 , 258 , 259 , 260 , 261 , 262 , 263 , 264 , 265 , 266 , 267 , 268 , 269 , 270 , 271 , 272 , 273 , 274 , 275 , 276 , 277 , 278 , 279 , 280 , 281 , 282 , 283 , 284 , 285 , 286 , 287 , 288 , 289 , 290 , 291 , 292 , 293 , 294 , 295 , 296 , 297 , 298 , 299 , 300 ]. The aberrant phenotype is the result of the modulation of typical pathways playing key roles in cell survival [ 255 , 259 , 263 , 265 , 283 ], apoptosis [ <...…”

“…Another important pathway in cancer is the phosphoinositide 3-kinase-AKT-mammalian target of the rapamycin (PI3K-AKT-mTOR) pathway, which is frequently hyperactivated in cancer and is essential for tumor cell growth and survival [ 61 ]. Indeed, several lncRNAs such as HOTAIR, HOXD-AS1, LINC00511, H19, and LINC01554, by targeting specific miRs, increase the expression of AKT and mTOR, promoting aberrant phenotypes [ 262 , 264 , 271 , 274 , 278 , 287 , 296 ].…”