PMID- 35339759 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220616 IS - 1980-5322 (Electronic) IS - 1807-5932 (Print) IS - 1807-5932 (Linking) VI - 77 DP - 2022 TI - microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene. PG - 100026 LID - S1807-5932(22)00022-9 [pii] LID - 10.1016/j.clinsp.2022.100026 [doi] LID - 100026 AB - OBJECTIVES: Accumulating research have reported that microRNAs (miRNAs) play important roles in Retinoblastoma (RB). Nonetheless, the function and underlying mechanism of miR-181a-5p in RB remain ambiguous. METHODS: The relative expression levels of miR-181a-5p and NRAS mRNA were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). RB cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) and 5'-Bromo-2'-deoxyuridine (BrdU) assays. Transwell assays and flow cytometry were performed to detect the migration, invasion, and apoptosis of RB cells. The interaction between miR-181a-5p and NRAS was explored using luciferase experiments, western blotting, and qRT-PCR. RESULTS: miR-181a-5p expression was found to be decreased in RB tissues and cell lines, and its expression was correlated with unfavorable pathological features of the patients. In vitro experiments revealed that miR-181a-5p reduced RB cell proliferation, migration, and invasion while enhancing apoptosis. Further research confirmed that NRAS is a direct target of miR-181a-5p. miR-181a-5p inhibited NRAS expression at both the mRNA and protein levels. Co-transfection of pcDNA-NRAS or NRAS small interfering RNA (siRNA) reversed the effects of miR-181a-5p mimics or miR-181a-5p inhibitors on RB cells. CONCLUSION: miR-181a-5p was significantly downregulated during the development of RB, and it suppressed the malignant behaviors of RB cells by targeting NRAS. CI - Copyright (c) 2022 HCFMUSP. Published by Elsevier Espana, S.L.U. All rights reserved. FAU - Ouyang, Ming AU - Ouyang M AD - Shenzhen Eye Hospital, Jinan University, China. Electronic address: taohe792@163.com. FAU - Liu, Guiqin AU - Liu G AD - Shenzhen Eye Hospital, Jinan University, China. FAU - Xiong, Cheng AU - Xiong C AD - Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, School of Optometry, Shenzhen University, China. FAU - Rao, Jing AU - Rao J AD - Shenzhen Eye Hospital, Shenzhen Eye Institute, Jinan University, School of Optometry, Shenzhen University, China. LA - eng PT - Journal Article DEP - 20220324 PL - United States TA - Clinics (Sao Paulo) JT - Clinics (Sao Paulo, Brazil) JID - 101244734 RN - 0 (MIrn181 microRNA, human) RN - 0 (Membrane Proteins) RN - 0 (MicroRNAs) RN - EC 3.6.1.- (GTP Phosphohydrolases) RN - EC 3.6.1.- (NRAS protein, human) SB - IM MH - Cell Line, Tumor MH - Cell Movement/genetics MH - Cell Proliferation/genetics MH - GTP Phosphohydrolases/genetics MH - Humans MH - Membrane Proteins/genetics MH - *MicroRNAs/genetics MH - Neoplasm Invasiveness/genetics MH - Proto-Oncogenes MH - *Retinal Neoplasms/genetics MH - *Retinoblastoma/genetics/pathology PMC - PMC8961171 OTO - NOTNLM OT - NRAS OT - Retinoblastoma OT - miR-181a-5p COIS- Conflicts of interest The authors declare no conflicts of interest. EDAT- 2022/03/28 06:00 MHDA- 2022/04/05 06:00 PMCR- 2022/03/24 CRDT- 2022/03/27 20:22 PHST- 2021/05/19 00:00 [received] PHST- 2021/08/16 00:00 [accepted] PHST- 2022/03/27 20:22 [entrez] PHST- 2022/03/28 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2022/03/24 00:00 [pmc-release] AID - S1807-5932(22)00022-9 [pii] AID - 100026 [pii] AID - 10.1016/j.clinsp.2022.100026 [doi] PST - epublish SO - Clinics (Sao Paulo). 2022 Mar 24;77:100026. doi: 10.1016/j.clinsp.2022.100026. eCollection 2022.