LINC00460 promotes pancreatic cancer progression by sponging miR‐491‐5p

Abstract

Background: A growing body of studies have suggested that LINC00460 is instrumental in tumorigenesis and tumour progression. Nonetheless, the biological function and mechanisms of LINC00460 in pancreatic ductal adenocarcinoma (PDAC) remain vague.Methods: Analysis based on public databases and a quantitative reverse transcriptionpolymerase chain reaction were performed to screen for differentially expressed lncRNAs in PDAC and to detect LINC00460 expression in PDAC cell lines and clinical samples. The survival of patients in the up-regulated and down-regulated LINC00460 expression groups was compared by using the Kaplan-Meier method. In addition, the potential biological functions of LINC00460 in PDAC were explored by cell counting kit-8, colony formation, flow cytometry and transwell assays. Furthermore, bioinformatics analysis, luciferase reporter assays and rescue experiments were applied to demonstrate the mechanism by which LINC00460 could directly bind to and inhibit miR-491-5p.Results: LINC00460 is up-regulated in PDAC and correlates with adverse survival outcomes. The results of functional tests verified that LINC00460 knockdown inhibited both cell proliferation and cell migration. Additionally, knockdown led to G0/G1 cell cycle blockage and enhanced cell apoptosis. Mechanistic investigations revealed that LINC00460 directly binds to and attenuates the tumour suppressor miR-491-5p, thus accelerating PDAC progression.Conclusions: This research showed that LINC00460 is overexpressed in PDAC and correlates with adverse clinical outcomes. Additionally, LINC00460 promotes the aggressiveness of PDAC by targeting miR-491-5p. Thus, LINC00460 may serve as diagnostic biomarker of PDAC and a new target for PDAC therapy.

Identification of a Prognostic Model Based on Fatty Acid Metabolism-Related Genes of Head and Neck Squamous Cell Carcinoma

“…LINC00460 (long intergenic non-protein coding RNA 460) is located on chromosome 13q33.2 and transcribed as a 913-nt transcript. Some studies showed that LINC00460 could promote tumor growth and malignant progression and is correlated with survival in multiple tumor types, including nasopharyngeal carcinoma, papillary thyroid carcinoma, esophageal cancer, gastric cancer, lung cancer, breast cancer, colorectal cancer, renal cell carcinoma, pancreatic cancer, bladder and urothelial carcinoma, ovarian cancer, and meningioma ( Kong et al, 2018 ; Liu W. et al, 2018 ; Liu X. et al, 2018 ; Wang F. et al, 2018 ; Xing et al, 2018 ; Wen et al, 2019 ; Ye et al, 2019 ; Cisneros-Villanueva et al, 2021 ; Hou et al, 2021 ; Qian et al, 2021 ; Wu et al, 2021 ; Yang et al, 2021 ). HNSCC is certainly no exception, with its identification as a prognostic lncRNA signature using orthogonal partial least squares discriminant analysis (OPLS-DA) which integrates RNA-Seq data from TCGA database and matching clinical information from a large cohort of patients with HNSCC( Cao et al, 2017 ).…”

LncRNA LINC00460: Function and mechanism in human cancer

“…48 Knockdown of LINC00460 decreased the expression of FADS1 and increased miR-1224-5p regulating the cell proliferation and migration in OS. 49 Knockdown of LINC00460 suppressed NPC cell proliferation, migration, and invasion by targeting miR-30a-3p/Rap1A and miR-149-5p/IL6 50,51 ; LINC00460 promoted OC progression by binding miR-338-3p 52 ; LINC00460 prompted bladder urothelial carcinoma progression via sponging of miR-612 by elevating FOXK1 expression 53 ; LINC00460 accelerated pancreatic cancer by binding to the suppressor miR-491-5p 54 ; knockdown of LINC00460 suppressed proliferation cervical cancer cells by targeting miR-503-5p and miR-361-3p/Gli1 axis 55,56 such as PIK3/AKT, Wnt/β-catenin, etc. The most common mechanism of action of LINC00460 in various tumors is the specific absorption of miRNA as ceRNA.…”

“…For bladder urothelial carcinoma, Li et al 53 indicated that the high expression of LINC00460 was associated with poor survival, promoted cell proliferation and migration, and LINC00460 prompted tumor progression via miR‐612/FOXK1 axis. Moreover, LINC00460 accelerated PC by binding to miR‐491‐5p 54 . For cervical cancer, LINC00460 affected tumor progression by targeting miR‐503‐5p, 55 or by mediating the miR‐361‐3p/Gli1 axis 56 .…”

“…Moreover, LINC00460 accelerated PC by binding to miR-491-5p. 54 For cervical cancer, LINC00460 affected tumor progression by targeting miR-503-5p, 55 or by mediating the miR-361-3p/ Gli1 axis. 56 Therefore, LINC00460 acts as a ceRNA in the pathogenesis and tumorigenesis of cancers base on the above research.…”

Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities

“…The following supporting information can be downloaded at: , Table S1: List of ncRNAs that could be used as therapeutic targets or biomarkers for gastric cancer [ 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 , 159 , 160 , 161 , 162 , 163 , 164 , 165 , 166 , 167 , 168 , 169 ]; Table S2: List of ncRNAs that could be used as therapeutic targets or biomarkers for pancreatic cancer [ 170 , 171 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 ,…”