Rong Li, Li Haiyu, Li Zhaodong, Ouyang Jing, Ma Yongping, Song Fangzhou, Chen Yaokai
Chongqing Public Health Medical Center, Chongqing, China.
Chongqing Medical University, Chongqing, China.
Front Med (Lausanne). 2020 Dec 4;7:608441. doi: 10.3389/fmed.2020.608441. eCollection 2020.
Chemotherapy and radiotherapy are effective treatment options for cervical cancer (CC), but their efficacy is limited by short survival rate of about 5 years particularly for advance stage CC. Bioinformatics analysis combined with experimental and data can identify potential markers of tumorigenesis and cancer progression to improve CC prognosis and survival rate of the patients. This study aims to investigate the prognostic value of family with sequence similarity 83, member A (FAM83A) gene and miR-206 in promoting CC progression and the involved genetic signaling pathways. This was a bioinformatic analysis study based on RNA sequencing data of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and verification by and experimental data. It was designed to evaluate whether the aberrantly expressed gene signatures could serve as new potential biomarker to improve prognosis prediction in CC. The TCGA RNA sequencing data [306 cervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma samples and 13 adjacent samples] and GEO data (GSE9750 and GSE52903 datasets) were integrated and performed a bioinformatics analysis. The results showed that CC-associated FAM83A gene serves as a key regulator of CC development and progression. Functionally, we observed that FAM83A is significantly overexpressed in CC, which is linked to poor overall survival as well as disease-free survival in CC patients. The and assessments performed after silencing FAM83A revealed that cell proliferation was significantly inhibited and the S-phase cell cycle arrest was induced. Mechanistically, FAM83A plays a role in PI3K/AKT signaling, and its downstream molecules could promote CC cell proliferation. Furthermore, functionality assessments by luciferase reporter system and immunoblot analysis showed that miR-206 was the upstream of FAM83A and negatively correlated with FAM83A. The miR-206/FAM83A/PI3K/AKT signaling pathway possibly serves as a critical effector in CC progression indicating the potential prognostic value of FAM83A gene as a novel biomarker for CC progression.
化疗和放疗是宫颈癌（CC）的有效治疗选择，但它们的疗效受到约5年的短生存率限制，特别是对于晚期CC。生物信息学分析结合实验和数据可以识别肿瘤发生和癌症进展的潜在标志物，以改善CC患者的预后和生存率。本研究旨在探讨序列相似性家族83成员A（FAM83A）基因和miR-206在促进CC进展中的预后价值以及所涉及的遗传信号通路。这是一项基于癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的RNA测序数据的生物信息学分析研究，并通过实验数据进行验证。其旨在评估异常表达的基因特征是否可作为新的潜在生物标志物来改善CC的预后预测。整合了TCGA RNA测序数据[306例宫颈鳞状细胞癌（SCC）和宫颈内膜腺癌样本以及13例相邻样本]和GEO数据（GSE9750和GSE52903数据集）并进行了生物信息学分析。结果表明，与CC相关的FAM83A基因是CC发生和进展的关键调节因子。在功能上，我们观察到FAM83A在CC中显著过表达，这与CC患者的总体生存率低以及无病生存率低有关。沉默FAM83A后进行的评估显示细胞增殖受到显著抑制并且诱导了S期细胞周期停滞。从机制上讲，FAM83A在PI3K/AKT信号传导中起作用，其下游分子可促进CC细胞增殖。此外，通过荧光素酶报告系统和免疫印迹分析进行的功能评估表明，miR-206是FAM83A的上游，并且与FAM83A呈负相关。miR-206/FAM83A/PI３K/AKT信号通路可能是CC进展中的关键效应因子，表明FAM83A基因作为CC进展的新型生物标志物具有潜在的预后价值。
