Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin, 150081, Hei Longjiang Province, China.
Harbin Medical University, 157 Baojian Road, Nangang District, Harbin, 150081, Hei Longjiang Province, China.
J Ovarian Res. 2021 Jan 7;14(1):6. doi: 10.1186/s13048-020-00756-y.
Ovarian cancer (OC) is one of the most aggressive women cancers with increasing incidence and mortality rates worldwide. Long non-coding RNAs (lncRNAs) could as major players in OC process. Although FAM83H antisense RNA1 (FAM83H-AS1) is demonstrated play an important roles in a many cancers, the detailed function and mechanism has not been reported in OC.
We integrated multiple kinds of bioinformatics approaches and experiments validated method to evaluate functions of FAM83H-AS1 in OC. Some differential expressed lncRNAs were identified between OC and normal control tissues. FAM83H-AS1 was one of most differentially expressed lncRNAs and up-regulated in multiple cancer types. Specially, expression of FAM83H-AS1 was higher in OC and showed difference in diverse stages. High FAM83H-AS1 expression is associated with worse pan-cancer and OC outcomes. FAM83H-AS1-centric network including lncRNA-miRNA, lncRNA-protein and lncRNA-mRNA ceRNA network were constructed to infer the function and mechanism of FAM83H-AS1. There were two methylation sites including cg01399317 and cg20519035 located at FAM83H-AS1. The methylation level of cg01399317 was correlated with gene expression of FAM83H-AS1. The expression level of FAM83H-AS1 was correlated with infiltration level of immune cell including macrophage, neutrphil and dendritic cell in OC patients. Lastly, qRT-PCR showed that the expression of FAM83H-AS1 was higher in OC tissues than normal control tissues.
Collectively, these results indicated that FAM83H-AS1 may act as an oncogenic driver and it may be a potential therapy target in OC.
卵巢癌（OC）是一种侵袭性最强的女性癌症，全球发病率和死亡率呈上升趋势。长链非编码 RNA（lncRNA）可能是 OC 发生发展过程中的重要调控因子。尽管 FAM83H 反义 RNA1（FAM83H-AS1）在许多癌症中发挥重要作用，但在 OC 中其详细功能和机制尚未报道。
我们综合运用多种生物信息学方法和实验验证方法，评估 FAM83H-AS1 在 OC 中的功能。鉴定出 OC 与正常对照组织之间存在差异表达的 lncRNA。FAM83H-AS1 是差异表达最显著的 lncRNA 之一，在多种癌症类型中上调。特别地，FAM83H-AS1 在 OC 中的表达水平较高，且在不同分期之间存在差异。FAM83H-AS1 高表达与泛癌和 OC 不良预后相关。构建 FAM83H-AS1 为中心的 lncRNA-miRNA、lncRNA-蛋白和 lncRNA-mRNA ceRNA 网络，推断 FAM83H-AS1 的功能和作用机制。FAM83H-AS1 上有两个甲基化位点，包括 cg01399317 和 cg20519035。cg01399317 的甲基化水平与 FAM83H-AS1 的基因表达相关。FAM83H-AS1 的表达水平与 OC 患者中巨噬细胞、中性粒细胞和树突状细胞等免疫细胞的浸润水平相关。最后，qRT-PCR 显示 OC 组织中 FAM83H-AS1 的表达高于正常对照组织。
综上所述，这些结果表明 FAM83H-AS1 可能作为一种癌基因驱动因子，可能成为 OC 的潜在治疗靶点。
