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miRNA-142-3p 通过直接靶向 FAM83D 在卵巢癌的发展中发挥潜在的肿瘤抑制作用。

miRNA-142-3p functions as a potential tumor suppressor directly targeting FAM83D in the development of ovarian cancer.

机构信息

Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Department of Ultrasound, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

出版信息

Aging (Albany NY). 2022 Apr 22;14(8):3387-3399. doi: 10.18632/aging.203998.

Abstract

BACKGROUND

FAM83D (family with sequence similarity 83, member D) is of particular interest in tumorigenesis and tumor progression. Ovarian cancer is the leading cause of cancer-related death in women all over the world. This study aims to research the association between FAM83D and ovarian cancer (OC).

METHODS

The gene expression data of OC and normal samples (GSE81873 and GSE27651) was downloaded from Gene Expression Omnibus (GEO) dataset. The bioinformatics analysis was performed to distinguish two differentially expressed genes (DEGs), prognostic candidate genes and functional enrichment pathways. Immunohistochemistry (IHC), Quantitative Real-time PCR (qPCR), and luciferase reporter assays were utilized for further study.

RESULTS

There were 56 DEMs and 63 DEGs in cancer tissues compared to normal tissues. According to the km-plot software, hsa-miR-142-3p and FAM83D were associated with the overall survival of patients with OC. Besides, Multivariate analysis included that hsa-miR-142-3p and FAM83D were independent risk factors for OC patients. Furthermore, qPCR demonstrated that miRNA-142-3p and FAM83D were differentially expressed in normal ovarian tissues (NOTs) and ovarian cancer tissues (OCTs). IHC results indicated that FAM83D was overexpressed in OCTs compared with NOTs. Last but not least, luciferase reporter assays verified that FAM83D was a direct target of hsa-miRNA-142-3p in OC cells.

CONCLUSIONS

The prognostic model based on the miRNA-mRNA network could provide predictive significance for the prognosis of OC patients, which would be worthy of clinical application. Our results concluded that miR-142-3p and its targets gene FAM83D may be potential diagnostic and prognostic biomarkers for patients with OC.

摘要

背景

FAM83D(家族与序列相似性 83,成员 D)在肿瘤发生和肿瘤进展中特别引人注目。卵巢癌是全世界女性癌症相关死亡的主要原因。本研究旨在研究 FAM83D 与卵巢癌(OC)之间的关系。

方法

从基因表达综合数据库(GEO)数据集下载 OC 和正常样本的基因表达数据(GSE81873 和 GSE27651)。进行生物信息学分析以区分两个差异表达基因(DEG)、预后候选基因和功能富集途径。免疫组织化学(IHC)、定量实时 PCR(qPCR)和荧光素酶报告基因测定用于进一步研究。

结果

与正常组织相比,癌症组织中有 56 个 DEMs 和 63 个 DEGs。根据 km-plot 软件,hsa-miR-142-3p 和 FAM83D 与 OC 患者的总生存率相关。此外,多变量分析包括 hsa-miR-142-3p 和 FAM83D 是 OC 患者的独立危险因素。此外,qPCR 表明 miRNA-142-3p 和 FAM83D 在正常卵巢组织(NOTs)和卵巢癌组织(OCTs)中表达不同。IHC 结果表明,与 NOTs 相比,FAM83D 在 OCTs 中过度表达。最后但并非最不重要的是,荧光素酶报告基因测定验证了 FAM83D 是 OC 细胞中 hsa-miRNA-142-3p 的直接靶标。

结论

基于 miRNA-mRNA 网络的预后模型可为 OC 患者的预后提供预测意义,值得临床应用。我们的结果表明,miR-142-3p 及其靶基因 FAM83D 可能是 OC 患者潜在的诊断和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee42/9085228/f542fe0ac518/aging-14-203998-g001.jpg

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