RETRACTED: Exosome-Derived miR-486-5p Regulates Cell Cycle, Proliferation and Metastasis in Lung Adenocarcinoma via Targeting NEK2

Abstract

Objective: This study aimed to describe the mechanism of exosome-derived miR-486-5p underlying the cell cycle and progression in lung adenocarcinoma (LUAD). Methods: Bioinformatics methods were applied for identifying the differentially expressed genes (DEGs) in the GEO-LUAD dataset, predicting where the potential target miRNA was expressed and exploring the corresponding downstream target mRNA. qRT-PCR was conducted to detect the levels of the target genes in cancer cells. Thereafter, a series of in vitro experiments were performed for cell activities evaluation, including CCK-8, EdU, colony formation assay and transwell. Besides, Western blot was applied to determine the protein levels of the migration and invasion-related factors (NEK2, E-cadherin, N-cadherin, Vimentin, MMP-2, and MMP-9). Dual-luciferase reporter gene assay was employed for validating the targeted relationship between the target genes. Furthermore, nude mouse transplantation tumor experiment was conducted to further validate the role of the target miRNA in tumor development, and immunohistochemistry was used for Ki67 detection and TUNEL was applied for cell apoptosis assay. Results: miR-486-5p was observed to be enriched in serum exosomes, and seen to be significantly down-regulated in cancer tissues as well as in cancer serum exosomes. It was proven that exosomes could release miR-486-5p, thus regulating LUAD progression and affecting cell cycle. Moreover, NEK2 was identified as a target of miR-486-5p both in vivo and in vitro. Enrichment analysis revealed that NEK2 was mainly activated in cell cycle and mitosis-related pathways. Meanwhile, NEK2 was found to present significant difference in different TNM stages. Furthermore, rescue experiments indicated that the inhibitory effect of miR-486-5p overexpression on LUAD progression could be abrogated when miR-486-5p and NEK2 were simultaneously up-regulated. Conclusion: Exosome-derived miR-486-5p is responsible for cell cycle arrest as well as the inhibition of cell proliferation and metastasis in LUAD via targeting NEK2.

Fusion-Independent Satellite Cell Communication to Muscle Fibers During Load-Induced Hypertrophy

“…We recently showed that miR-206 is transferred by satellite cell EVs to fibrogenic cells during MOV to regulate collagen deposition, 7 and confirm here that miR-206 is the most abundant miRNA in MPC EVs ( Figure 2C ). Expanding on our earlier work, we found numerous miRNAs enriched in MPC EVs ( Figure 2C ) that are experimentally shown to lower Mmp9 expression, such as miR-24, 47–49 miR-149, 50–55 and miR-486, 56 , 57 as well as miRNAs that are validated to target the 3′-UTR of Mmp9 mRNA and reduce transcript levels, including Let-7e, 58 miR-133a and -133b, 59 , 60 and miR-320 61 ( Figure 2D ). In silico predicted miRNA-mRNA target analysis 62 further revealed that ECM remodeling is the most regulated process by MPC EV miRNAs ( Figure 2E , Tables S2 and S3 ).…”

Analysis of m6A RNA Methylation-Related Genes in Liver Hepatocellular Carcinoma and Their Correlation with Survival

“…DNA topoisomerase 2-alpha ( TOP2A ), exodeoxyribonuclease 1 ( EXO1 ), serine/threonine-protein kinase Nek2 ( NEK2 ), baculoviral IAP repeat-containing protein 5 ( BIRC5 ), hyaluronan mediated motility receptor ( HMMR ), structural maintenance of chromosomes protein 4 ( SMC4 ), bloom syndrome protein ( BLM ), casein kinase I isoform epsilon ( CSNK1E ), cytoskeleton-associated protein 5 ( CKAP5 ), and inner centromere protein ( INCENP ) were identified as the hub genes based on the degrees of nodes which were more than 10 ( Figure 2 a) [ 11 ]. TOP2A , EXO1 , NEK2 , BIRC5 , SMC4 , BLM , CSNK1E , CKAP5 , and INCENP were related to DNA replication and cell division, and HMMR was related to cell motility [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. The detailed functions of the hub genes are described in the discussion section and Supplementary Table S3 .…”

“…Furthermore, current reports have showed NEK2, as an important cyclin, has the functions of regulating the assembly and separation of centrosomes, the formation of spindles, and the precise separation of chromosomes [ 16 , 17 ]. In addition, NEK2 may also become an important marker for tumor differentiation and prognosis detection, and is an important potential target for cancer treatment [ 18 ].…”

MiR‐423‐5p aggravates lung adenocarcinoma via targeting CADM1

“…Despite developments in clinical oncology technology, the prognosis for patients with LUAD is very poor 5 . Meanwhile, because of lack of effective biomarkers and not immediately apparent early symptoms, the clinical therapy available for LUAD is still disappointing 6,7 . Hence, it is essential that the progress of LUDA related gene expression and the molecular mechanism for early diagnosis and treatment is explored.…”