Department of Otolaryngology-Head & Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China.
Anhui Medical University, Hefei, People's Republic of China.
Cancer Med. 2023 Mar;12(5):5703-5717. doi: 10.1002/cam4.5315. Epub 2022 Oct 11.
As one of the most devastating cancers, head and neck squamous cell carcinoma (HNSCC) has a short survival time and poor prognosis. Pescadillo ribosomal biogenesis factor 1 (PES1) plays a critical role in the progression of numerous cancers. However, its role and underlying mechanisms in HNSCC remain unclear.
A variety of bioinformatic approaches were used to identify the expressions, prognostic and diagnostic value of PES1 in HNSCC. qRT-PCR, immunofluorescence (IF) assay, western blotting and immunohistochemical (IHC) were used to evaluate the expression of PES1 in HNSCC cell lines and clinical tissues. PES1 was knocked down in TU177 and FaDu cells which have high PES1 expression. The effects of PES1 on cell proliferation and tumour growth in HNSCC were elevated by colony formation, CCK8 assays and tumorigenicity assay in nude mice. The effects on cisplatin (CDDP) sensitivity upon silencing of PES1 were assessed using a patient-derived xenograft (PDX) model.
PES1 expression was an independent prognostic factor for HNSCC and negatively associated with the overall survival rate. Silencing of PES1 reduces HNSCC cell proliferation and tumour growth. Moreover, PES1 inhibition significantly sensitises HNSCC cells to cisplatin. Furthermore, we found a PES1 has a high correlation with c-Myc and plays an essential role in the tumour immune microenvironment.
Our findings suggest that PES1 is associated with tumour growth and drug resistance and served as a potential cancer marker for diagnosis and a putative therapeutic target for HNSCC.
作为最具破坏性的癌症之一，头颈部鳞状细胞癌（HNSCC）的存活时间短，预后差。Pescadillo 核糖体生物发生因子 1（PES1）在许多癌症的进展中起着关键作用。然而，其在 HNSCC 中的作用和潜在机制尚不清楚。
使用多种生物信息学方法来鉴定 PES1 在 HNSCC 中的表达、预后和诊断价值。使用 qRT-PCR、免疫荧光（IF）检测、Western blot 和免疫组织化学（IHC）评估 PES1 在 HNSCC 细胞系和临床组织中的表达。在 PES1 高表达的 TU177 和 FaDu 细胞中敲低 PES1。在裸鼠中通过集落形成、CCK8 检测和致瘤性检测来提高 PES1 对 HNSCC 细胞增殖和肿瘤生长的影响。使用患者来源的异种移植（PDX）模型评估沉默 PES1 对顺铂（CDDP）敏感性的影响。
PES1 表达是 HNSCC 的独立预后因素，与总生存率呈负相关。沉默 PES1 可降低 HNSCC 细胞的增殖和肿瘤生长。此外，PES1 抑制可显著增强 HNSCC 细胞对顺铂的敏感性。此外，我们发现 PES1 与 c-Myc 高度相关，在肿瘤免疫微环境中发挥重要作用。
我们的研究结果表明，PES1 与肿瘤生长和耐药性相关，可作为潜在的癌症诊断标志物和 HNSCC 的潜在治疗靶点。
