Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, People's Republic of China.
Genes Genomics. 2024 Jan;46(1):49-64. doi: 10.1007/s13258-023-01463-w. Epub 2023 Nov 20.
Previous studies indicate that the splicing process, regulated by the cellular machinery of tumors (spliceosome), undergoes alterations, leading to oncogenic splicing events associated with the progression of tumors towards aggressiveness. However, the role of serine/arginine-rich splicing factor 7 (SRSF7) in hepatocellular carcinoma (HCC) and the tumor microenvironment (TME) remains unclear.
This study was aimed to explore the role and clinical significance of SRSF7 in HCC. By conducting functional analysis and gene set enrichment analysis, it was discovered that SRSF7 contributes to multiple pathways associated with immune response and tumor advancement. Further experiments verified that silencing of SRSF7 obviously inhibits progression of HCC.
Aberrant expression of SRSF7, which were referred as an independent prognostic risk factor, effectively predicts the prognosis of patients with HCC. Functional and gene enrichment analyses revealed that SRSF7 is linked with multiple immune and tumor progression-related pathways, including the B cell receptor signaling pathway, positive regulation of leukocyte and immunoglobulin receptor binding cell activation, nuclear division, membrane invagination, cell cycle, as well as mTOR signaling pathway. Furthermore, increased SRSF7 expression was associated with tumor-infiltrating inflammatory cells (CD4+, monocytes/macrophages, CD8 + and endothelial). Additionally, multiple immune checkpoint genes were markedly positively related to SRSF7. The efficiency of SRSF7 in predicting immunomodulator and chemokine responses were also assessed in microenvironment. Moreover, in vitro analyses demonstrated that knockdown of SRSF7 suppressed the malignant evolution of HCC possibly by deactivating the PI3K/AKT/mTOR signaling.
The role of SRSF7 in the tumor microenvironment has been successfully assessed. It may be a valid bio-index for predicting the HCC prognosis, thereby guiding individualized immunotherapy for cancer.
先前的研究表明，细胞肿瘤机制（剪接体）调控的剪接过程会发生改变，导致与肿瘤向侵袭性进展相关的致癌性剪接事件。然而，丝氨酸/精氨酸丰富剪接因子 7（SRSF7）在肝细胞癌（HCC）和肿瘤微环境（TME）中的作用尚不清楚。
本研究旨在探讨 SRSF7 在 HCC 中的作用和临床意义。通过功能分析和基因集富集分析，发现 SRSF7 有助于与免疫反应和肿瘤进展相关的多种途径。进一步的实验验证表明，沉默 SRSF7 明显抑制 HCC 的进展。
SRSF7 的异常表达被认为是一个独立的预后危险因素，有效地预测了 HCC 患者的预后。功能和基因富集分析表明，SRSF7 与多种免疫和肿瘤进展相关途径有关，包括 B 细胞受体信号通路、白细胞和免疫球蛋白受体结合细胞激活的正调控、核分裂、膜内陷、细胞周期以及 mTOR 信号通路。此外，SRSF7 表达增加与肿瘤浸润性炎症细胞（CD4+、单核细胞/巨噬细胞、CD8+和内皮细胞）有关。此外，多个免疫检查点基因与 SRSF7 显著正相关。还在微环境中评估了 SRSF7 预测免疫调节剂和趋化因子反应的效率。此外，体外分析表明，SRSF7 的敲低可能通过使 PI3K/AKT/mTOR 信号失活来抑制 HCC 的恶性演变。
成功评估了 SRSF7 在肿瘤微环境中的作用。它可能是预测 HCC 预后的有效生物指标，从而指导癌症的个体化免疫治疗。
