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构建竞争性内源性RNA相互作用网络作为转移性黑色素瘤的预后标志物

Construction of competing endogenous RNA interaction network as prognostic markers in metastatic melanoma.

作者信息

He Zan, Xin Zijuan, Peng Yongfei, Zhao Hua, Fang Xiangdong

机构信息

Department of Dermatology, General Hospital of People's Liberation Army, Beijing, China.

Medical School of Chinese People's Liberation Army, Beijing, China.

出版信息

PeerJ. 2021 Sep 15;9:e12143. doi: 10.7717/peerj.12143. eCollection 2021.

Abstract

Malignant melanoma (MM) is a malignant tumor originating from melanocytes, with high aggressiveness, high metastasis and extremely poor prognosis. MM accounts for 4% of skin cancers and 80% of mortality, and the median survival of patients with metastatic melanoma is only about 6 months, with a five-year survival rate of less than 10%. In recent years, the incidence of melanoma has gradually increased and has become one of the serious diseases that endanger human health. Competitive endogenous RNA (ceRNA) is the main model of the mechanism by which long chain non-coding RNAs (lncRNAs) play a regulatory role in the disease. LncRNAs can act as a "sponge", competitively attracting small RNAs (micoRNAs; miRNAs), thus interfering with miRNA function, and affect the expression of target gene messenger RNAs (mRNAs), ultimately promoting tumorigenesis and progression. Bioinformatics analysis can identify potentially prognostic and therapeutically relevant differentially expressed genes in MM, finding lncRNAs, miRNAs and mRNAs that are interconnected through the ceRNA network, providing further insight into gene regulation and prognosis of metastatic melanoma. Weighted co-expression networks were used to identify lncRNA and mRNA modules associated with the metastatic phenotype, as well as the co-expression genes contained in the modules. A total of 17 lncRNAs, six miRNAs, and 11 mRNAs were used to construct a ceRNA interaction network that plays a regulatory role in metastatic melanoma patients. The prognostic risk model was used as a sorter to classify the survival prognosis of melanoma patients. Four groups of ceRNA interaction triplets were finally obtained, which miR-3662 might has potential implication for the treatment of metaststic melanoma patients, and futher experiments confirmed the regulating relationship and phenotype of this assumption. This study provides new targets to regulate metastatic process, predict metastatic potential and indicates that the miR-3662 can be used in the treatment of melanoma.

摘要

恶性黑色素瘤(MM)是一种起源于黑素细胞的恶性肿瘤,具有高侵袭性、高转移性且预后极差。MM占皮肤癌的4%,但死亡率却占80%,转移性黑色素瘤患者的中位生存期仅约6个月,五年生存率不到10%。近年来,黑色素瘤的发病率逐渐上升,已成为危害人类健康的严重疾病之一。竞争性内源RNA(ceRNA)是长链非编码RNA(lncRNA)在疾病中发挥调控作用的主要机制模型。lncRNA可作为一种“海绵”,竞争性地吸附小RNA(微小RNA;miRNA),从而干扰miRNA功能,并影响靶基因信使RNA(mRNA)的表达,最终促进肿瘤发生和进展。生物信息学分析可识别MM中潜在的预后和治疗相关差异表达基因,找到通过ceRNA网络相互连接的lncRNA、miRNA和mRNA,为转移性黑色素瘤的基因调控和预后提供进一步的见解。加权共表达网络用于识别与转移表型相关的lncRNA和mRNA模块,以及模块中包含的共表达基因。共使用17种lncRNA、6种miRNA和11种mRNA构建了在转移性黑色素瘤患者中起调控作用的ceRNA相互作用网络。将预后风险模型用作分类器来对黑色素瘤患者的生存预后进行分类。最终获得了四组ceRNA相互作用三联体,其中miR-3662可能对转移性黑色素瘤患者的治疗具有潜在意义,进一步的实验证实了这一假设的调控关系和表型。本研究为调控转移过程、预测转移潜能提供了新靶点,并表明miR-3662可用于黑色素瘤的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b443/8449535/d5e6cfe1be8a/peerj-09-12143-g001.jpg

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