Sialylation promotes tumorigenesis by affecting various cancer-related events, including apoptosis inhibition, cell growth, invasion, migration, metastasis, chemo-resistance, and immunomodulation in favor of tumor progression. An altered expression of sialyltransferase enzymes is responsible for synthesizing various tumor-associated sialylated structures. In the present study, our findings have revealed a significant up-regulation of ST3Gal-4 transcript in the two major subtypes of NSCLC cell lines [squamous cell carcinoma cell line (NCI-H520) and adenocarcinoma cell line (A549)]. Thus, the role of the ST3Gal-4 gene was assessed on cancer-associated signal transduction pathways in these cells in view of proliferation, invasion, and migration. ST3Gal-4 was silenced by transfection of both the cell lines with esi-ST3Gal-4-RNA, which RT-PCR and western immunoblotting confirmed. Silencing of ST3Gal-4 resulted in a decreased expression of MAL-I interacting membrane-HSP60, identified earlier as an α2,3-sialylated glycoprotein, thus pointing towards the possible role of ST3Gal-4 in its sialylation. The proliferation, invasion, and migration of both types of NSCLC cells were reduced significantly in the ST3Gal-4 silenced cells. Our findings were substantiated by the down-regulation of β-catenin and E-cadherin, a reduced expression of activated AKT1, ERK1/2, and NF-ƙB in these cells. We propose that ST3Gal-4 may be the disease-associated sialyltransferase involved in α2,3 sialylation of the membrane proteins, including HSP60 of the NSCLC cells. This may lead to the conformational alteration of these proteins, required for the activation of E-cadherin/β-catenin, AKT, and ERK/NF-ƙB mediated signal transduction pathways in these cells, resulting in their proliferation, invasion, and migration.

唾液酸化通过影响各种癌症相关事件来促进肿瘤发生，包括细胞凋亡抑制、细胞生长、侵袭、迁移、转移、化学抗性和有利于肿瘤进展的免疫调节。唾液酸转移酶的表达改变负责合成各种与肿瘤相关的唾液酸化结构。在本研究中，我们的研究结果揭示了 ST3Gal-4 转录物在 NSCLC 细胞系的两种主要亚型 [鳞状细胞癌细胞系 (NCI-H520) 和腺癌细胞系 (A549)] 中的显着上调。因此，从增殖、侵袭和迁移的角度评估了 ST3Gal-4 基因对这些细胞中癌症相关信号转导通路的作用。通过用 esi-ST3Gal-4-RNA 转染两种细胞系使 ST3Gal-4 沉默，RT-PCR和蛋白质免疫印迹证实了这一点。ST3Gal-4 的沉默导致 MAL-1 相互作用膜 HSP60 的表达降低，早先被鉴定为 α2,3-唾液酸化糖蛋白，因此表明 ST3Gal-4 在其唾液酸化中的可能作用。在 ST3Gal-4 沉默细胞中，两种类型的 NSCLC 细胞的增殖、侵袭和迁移均显着降低。我们的研究结果得到了 β-catenin 和 E-cadherin 下调的证实，这些细胞中活化的 AKT1、ERK1/2 和 NF-ƙB 的表达降低。我们提出 ST3Gal-4 可能是与疾病相关的唾液酸转移酶，参与膜蛋白的 α2,3 唾液酸化，包括 NSCLC 细胞的 HSP60。这可能导致这些蛋白质的构象改变，这是激活 E-钙粘蛋白/β-连环蛋白、AKT、