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OPA相互作用蛋白5反义RNA 1通过FOXM1/ Wnt/β-连环蛋白通路促进胰腺癌细胞的迁移和侵袭

OPA Interacting Protein 5 Antisense RNA 1 Expedites Cell Migration and Invasion Through FOXM1/ Wnt/β-Catenin Pathway in Pancreatic Cancer.

作者信息

Shi Chengjian, Zhang Hang, Wang Min, Tian Rui, Li Xu, Feng Yechen, Peng Feng, Qin Renyi

机构信息

Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No 1095 Jiefang Avenue, Wuhan, 430030, China.

出版信息

Dig Dis Sci. 2022 Mar;67(3):915-924. doi: 10.1007/s10620-021-06919-1. Epub 2021 Mar 29.

Abstract

BACKGROUND

Pancreatic cancer (PC) is a digestive tract malignancy with poor prognosis. Long noncoding RNA (lncRNA) OPA interacting protein 5 antisense RNA 1 (OIP5-AS1) was regarded to be correlated with human malignancy, working as tumor suppressor or promoter on the basis of tumor types. However, the function of OIP5-AS1 in PC remained unclear.

AIMS

The study focused on the function and regulatory mechanism of OIP5-AS1 in PC.

METHODS

OIP5-AS1 expression was assessed by the quantitative reverse transcription PCR (RT-qPCR) in tumor tissues and PC cell lines. 5-ethynyl-2'-deoxyuridine (EdU) incorporation and cell counting kit-8 (CCK-8) assays were applied to detect cell proliferation ability. Through wound healing and transwell assays, cell migration and invasion capacities were estimated. Flow cytometry analysis was performed to examine apoptosis capability of PC cells.

RESULTS

OIP5-AS1 downregulating inhibited cell proliferation, migration, and invasion capacities, while promoting cell apoptosis rates. As a competing endogenous RNA (ceRNA), OIP5-AS1 competed with Forkhead Box M1 (FOXM1) for the binding sites on microRNA-320b (miR-320b). OIP5-AS1 was able to upregulate FOXM1 expression via silencing miR-320b. Furthermore, FOXM1 served as an activator of Wnt/β-catenin pathway and mediated the effect of OIP5-AS1 on Wnt/β-catenin pathway.

CONCLUSION

OIP5-AS1 expedites the proliferative, migrated, and invasive capability of PC cells, while repressing cell apoptosis through regulating miRNA-320b/FOXM1 axis and FOXM1/Wnt/β-catenin pathway in PC. OIP5-AS1 regulation on FOXM1/Wnt/β-catenin pathway may offer novel efficient markers for PC treatments.

摘要

背景

胰腺癌(PC)是一种预后较差的消化道恶性肿瘤。长链非编码RNA(lncRNA)OPA相互作用蛋白5反义RNA1(OIP5-AS1)被认为与人类恶性肿瘤相关,根据肿瘤类型可作为肿瘤抑制因子或促进因子。然而,OIP5-AS1在胰腺癌中的功能仍不清楚。

目的

本研究聚焦于OIP5-AS1在胰腺癌中的功能及调控机制。

方法

通过定量逆转录PCR(RT-qPCR)评估肿瘤组织和胰腺癌细胞系中OIP5-AS1的表达。采用5-乙炔基-2'-脱氧尿苷(EdU)掺入法和细胞计数试剂盒-8(CCK-8)检测细胞增殖能力。通过伤口愈合实验和Transwell实验评估细胞迁移和侵袭能力。采用流式细胞术分析检测胰腺癌细胞的凋亡能力。

结果

下调OIP5-AS1可抑制细胞增殖、迁移和侵袭能力,同时促进细胞凋亡率。作为一种竞争性内源性RNA(ceRNA),OIP5-AS1与叉头框M1(FOXM1)竞争微小RNA-320b(miR-320b)上的结合位点。OIP5-AS1能够通过沉默miR-320b上调FOXM1表达。此外,FOXM1作为Wnt/β-连环蛋白通路的激活剂,介导了OIP5-AS在Wnt/β-连环蛋白通路上的作用。

结论

OIP5-AS1通过调节miRNA-320b/FOXM1轴和FOXM1/Wnt/β-连环蛋白通路,促进胰腺癌细胞的增殖、迁移和侵袭能力,同时抑制细胞凋亡。OIP5-AS1对FOXM1/Wnt/β-连环蛋白通路的调控可能为胰腺癌治疗提供新的有效标志物。

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