Department of Pharmacy, Jining Medical University, Rizhao, Shandong, China.
Department of Pharmacy, Jining Medical University, Rizhao, Shandong, China.
Tissue Cell. 2022 Oct;78:101867. doi: 10.1016/j.tice.2022.101867. Epub 2022 Jul 16.
Pancreatic cancer (PC) is the seventh-leading cause of cancer-related mortality, and is associated with limited therapeutic options and poor prognosis. The extracellular matrix (ECM) represents the main component of the tumor microenvironment. Studies have found controversial roles of osteoglycin (OGN), a classical small leucine-rich proteoglycan found in the ECM in human malignancies; however, the significance of OGN in PC has not been determined. Here, the expression profiles of OGN in PC tissues and cell lines were evaluated by Gene Expression Profiling Interactive Analysis (GEPIA) database, immunohistochemistry, western blot, and quantitative PCR. OGN was found to be significantly upregulated in PC tissues and cell lines. Moreover, the expression of OGN was observed to be closely associated with TNM stage, stage III showed a higher OGN expression than that of stages I and II. Survival analysis showed that patients with PC showing high levels of OGN had low survival rates. The effects of OGN on cell proliferation and apoptosis were analyzed using MTT, CCK8, EdU and TUNEL assays. Wound-healing and invasion assays were conducted to test migratory and invasive abilities. Overexpression of OGN was demonstrated to promote proliferation, migration, and invasion, and inhibit apoptosis of PC cells. Further experiments revealed that inhibitor of DNA binding 4 (ID4) was upregulated by OGN. Silencing ID4 by small interfering RNA was shown to partially reverse the tumor-promoting effect of OGN. Collectively, our preliminary results indicate that the elevated expression of OGN may be associated with PC progression and may serve as a potential biomarker for the diagnosis and prognosis of PC. Targeting of OGN/ID4 axis may be a promising strategy in PC therapy.
胰腺癌（PC）是第七大癌症相关死亡原因，与治疗选择有限和预后不良有关。细胞外基质（ECM）代表肿瘤微环境的主要成分。研究发现，在人类恶性肿瘤中，经典的小富含亮氨酸的蛋白聚糖骨桥蛋白（OGN）在 ECM 中具有有争议的作用；然而，OGN 在 PC 中的意义尚未确定。在这里，通过基因表达谱分析交互分析（GEPIA）数据库、免疫组织化学、western blot 和定量 PCR 评估了 OGN 在 PC 组织和细胞系中的表达谱。发现 OGN 在 PC 组织和细胞系中显著上调。此外，OGN 的表达与 TNM 分期密切相关，III 期 OGN 表达高于 I 期和 II 期。生存分析表明，OGN 水平高的 PC 患者生存率较低。使用 MTT、CCK8、EdU 和 TUNEL 测定分析了 OGN 对细胞增殖和凋亡的影响。进行划痕愈合和侵袭测定以测试迁移和侵袭能力。过表达 OGN 被证明可促进 PC 细胞的增殖、迁移和侵袭，并抑制凋亡。进一步的实验表明，OGN 上调了 DNA 结合抑制因子 4（ID4）。用小干扰 RNA 沉默 ID4 可部分逆转 OGN 的促肿瘤作用。总之，我们的初步结果表明，OGN 的高表达可能与 PC 的进展有关，并且可能成为 PC 诊断和预后的潜在生物标志物。靶向 OGN/ID4 轴可能是 PC 治疗的一种有前途的策略。
