文献类型：期刊文献

中文题名：miR-18a-5p靶向调控RORA在结直肠癌增殖进展中的作用及临床意义

英文题名：miR-18a-5p Regulates Colorectal Cancer Proliferation and Progression by Targeting RORA

作者：陈一锋[1,2];王帅[1,2];柴明明[1,2];张迪[1,2,3];王春霞[1,2,3];赵丽霞[1,2,3];张洪来[1,2];杨熊飞[1,2];张维胜[1,2];王涛[1,2]

第一作者：陈一锋

机构：[1]甘肃省人民医院/国家卫生健康委胃肠肿瘤诊治重点实验室,兰州730000;[2]甘肃省人民医院肛肠科,兰州730000;[3]甘肃中医药大学第一临床医学院,兰州730000

第一机构：甘肃省人民医院/国家卫生健康委胃肠肿瘤诊治重点实验室,兰州730000

年份：2024

卷号：51

期号：8

起止页码：667

中文期刊名：肿瘤防治研究

外文期刊名：Cancer Research on Prevention and Treatment

收录：CSTPCD;;Scopus

基金：国家自然科学基金(82160522);国家卫生健康委员会胃肠道肿瘤诊疗重点实验室项目(NLDTG2020021);中国医学科学院中央级公益性科研院所基本科研业务费专项项目(2019PT320005);甘肃省自然科学基金(22JR5RA653);兰州市科技计划项目(2022-5-68)。

语种：中文

中文关键词：miR-18a-5p;RORA;结直肠癌;增殖

外文关键词：miR-18a-5p;RORA;Colorectal cancer;Proliferation

摘要：目的探讨miR-18a-5p和RORA在结直肠癌增殖中的作用机制及临床意义。方法采用qRT-PCR、FISH、IHC方法检测miR-18a-5p和RORA在结直肠癌细胞和组织中的表达情况。通过EdU和CFSE实验检测细胞增殖能力、FCM实验检测细胞凋亡情况,细胞划痕实验和Transwell侵袭实验检测细胞迁移和侵袭能力。进一步通过双荧光素酶报告实验、细胞功能挽救实验、RT-PCR和Western blot实验验证miR-18a-5p对RORA的靶向调控作用。最后运用生物信息学探究miR-18a-5p调控RORA促进结直肠癌恶性增殖和侵袭进展的分子机制。结果miR-18a-5p在结直肠癌组织和细胞中高表达(P<0.05),并且能够促进结直肠癌细胞的增殖、迁移和侵袭(P<0.05)。此外RORA是miR-18a-5p的靶基因,过表达RORA能够有效消减miR-18a-5p促结直肠癌细胞恶性生物学表型的作用(P<0.05)。RORA在结直肠癌组织中的表达与CD8+T细胞浸润及其表面标志蛋白CD8A的表达显著正相关(P<0.05)。结论miR-18a-5p可能通过靶向调控RORA促进结直肠癌的进展;miR-18a-5p/RORA调控通路可能参与了结直肠癌免疫微环境的塑造,是结直肠癌的潜在治疗靶点。
Objective To investigate the mechanism and clinical significance of miR-18a-5p and retinoid acid receptor-related orphan receptor-α(RORA)in the proliferation and progression of colorectal cancer(CRC)cells.Methods The expressions of miR-18a-5p and RORA in CRC cells and tissues were detected via qRT-PCR,FISH,and IHC.Cell proliferation capability was detected through EdU and CFSE assay,cell apoptosis by flow cytometry assay,and cell migration and invasion abilities by cell scratch and Transwell invasion assays,respectively.The targeted regulation of miR-18a-5p on RORA was further verified via dualluciferase reporter assay,cell function rescue test,RT-PCR,and Western blot assay.Finally,bioinformatics was used to explore the molecular mechanism of miR-18a-5p promoting malignant proliferation,invasion,and progression of CRC via regulating RORA.Results miR-18a-5p exhibited a high expression in CRC tissues and cells(P<0.05)and promoted the proliferation,migration,and invasion of CRC cells(P<0.05).In addition,RORA served as the target gene of miR-18a-5p,and its overexpression effectively reduced the promoting function of miR-18a-5p in the malignant biological phenotype of CRC cells(P<0.05).The expression of RORA in CRC tissues showed a significantly positively correlation with the infiltration of CD8+T cells and the expression of its surface marker protein CD8A.Conclusion The targeted regulation of RORA by miR-18a-5p promotes the proliferation and progression of CRC.The miR-18a-5p/RORA regulatory pathway possibly contributes to the immune microenvironment of CRC,which can be a potential therapeutic target for CRC.