Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Radiation Oncology, Guangxi Zhuang Autonomous Region People's Hospital, Nanning, Guangxi, China.
Hum Cell. 2022 Nov;35(6):1856-1868. doi: 10.1007/s13577-022-00771-9. Epub 2022 Aug 26.
Novel and accurate biomarkers are needed for early detection and progression evaluation of hepatocellular carcinoma (HCC). Protein phosphatase 1 regulatory subunit 1A (PPP1R1A) has been studied in cancer biology; however, the expression pattern and biological function of PPP1R1A in HCC are unclear. The differentially expressed genes (DEGs) in HCC were screened by The Cancer Genome Atlas (TCGA) database. Real-time PCR and immunohistochemistry (IHC) assay were used to detect the expression of PPP1R1A in BALB/c mice, human normal tissues and corresponding tumor tissues, especially HCC. Then, Kaplan-Meier analysis of patients with HCC was performed to evaluate the relationship between PPP1R1A expression and prognosis. The transcriptional regulatory network of PPP1R1A was constructed based on the differentially expressed mRNAs, microRNAs and transcription factors (TFs). To explore the downstream regulation of PPP1R1A, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis and immune infiltration score were performed. A total of 4 DEGs were screened out. PPP1R1A was differentially distributed and expressed in BALB/c mice and human tissues. PPP1R1A expression was higher in normal tissues than that in tumor tissues, and patients with higher PPP1R1A expression had better clinical outcome in HCC. In addition, we constructed miR-21-3p/TAL1/PPP1R1A transcriptional network. Furthermore, PPP1R1A may modulate the activation of PI3K-Akt pathway, cell cycle, glycogen metabolism and the recruitment of M2 macrophage in HCC. This study may help to clarify the function and mechanism of PPP1R1A in HCC and provide a potential biomarker for tumor prevention and treatment.
需要新型且准确的生物标志物来实现对肝细胞癌(HCC)的早期检测和进展评估。蛋白磷酸酶 1 调节亚基 1A(PPP1R1A)已在癌症生物学中进行了研究;然而,PPP1R1A 在 HCC 中的表达模式和生物学功能尚不清楚。通过癌症基因组图谱(TCGA)数据库筛选 HCC 中的差异表达基因(DEGs)。实时 PCR 和免疫组织化学(IHC)检测用于检测 BALB/c 小鼠、人正常组织和相应肿瘤组织(尤其是 HCC)中 PPP1R1A 的表达。然后,对 HCC 患者进行 Kaplan-Meier 分析以评估 PPP1R1A 表达与预后之间的关系。基于差异表达的 mRNAs、microRNAs 和转录因子(TFs)构建 PPP1R1A 的转录调控网络。为了探索 PPP1R1A 的下游调控,进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)功能富集分析和免疫浸润评分。筛选出 4 个 DEGs。PPP1R1A 在 BALB/c 小鼠和人组织中的分布和表达存在差异。PPP1R1A 在正常组织中的表达高于肿瘤组织,并且 PPP1R1A 表达较高的患者在 HCC 中具有更好的临床结局。此外,我们构建了 miR-21-3p/TAL1/PPP1R1A 转录网络。此外,PPP1R1A 可能调节 HCC 中 PI3K-Akt 通路、细胞周期、糖原代谢和 M2 巨噬细胞募集的激活。本研究可能有助于阐明 PPP1R1A 在 HCC 中的功能和机制,并为肿瘤的预防和治疗提供潜在的生物标志物。