Anhui Medical University, Hefei, Anhui 230032, P.R. China.
Department of Laboratory, The 904th Hospital of Joint Logistic Support Force of PLA, Wuxi, Jiangsu 214044, P.R. China.
Oncol Rep. 2021 Jun;45(6). doi: 10.3892/or.2021.8064. Epub 2021 Apr 28.
Golgi phosphoprotein 3 (GOLPH3) has been demonstrated to promote tumor progression in various gastrointestinal malignancies. However, its effects in gallbladder carcinoma (GBC) remain unknown. In the present study, the expression levels of GOLPH3 and nucleotide‑binding domain leucine‑rich repeat and pyrin domain containing receptor 3 (NLRP3) in human GBC tissues were detected by immunohistochemistry, and the clinical data and survival of these patients were analyzed. Next, whether GOLPH3 could affect tumor proliferation via regulation of the NLRP3 inflammasome was investigated . The results demonstrated that GOLPH3 could promote GBC cell proliferation, and that it regulated protein expression levels of NLRP3, as well as Caspase‑1 P10. Conversely, knockdown of NLRP3 reversed the effects of GOLPH3 overexpression on GBC cell proliferation. GOLPH3 and NLRP3 expression levels were found to be upregulated in GBC tissues and their expression was positively correlated. The expression of GOLPH3 and NLRP3 was associated with the expression of the proliferative marker Ki‑67 in tissues, and associated with poor survival, tumor stage, degree of differentiation, depth of invasion, carbohydrate antigen 19‑9 and C‑reactive protein levels in patients with GBC. In summary, these results indicate that GOLPH3 promotes GBC cell proliferation via a NLRP3/Caspase‑1 pathway. GOLPH3 and NLRP3 participate in the process of human GBC growth and may serve as a potential therapeutic targets.
高尔基磷酸蛋白 3（GOLPH3）已被证实可促进多种胃肠道恶性肿瘤的进展。然而，其在胆囊癌（GBC）中的作用尚不清楚。在本研究中，通过免疫组织化学检测了人 GBC 组织中 GOLPH3 和核苷酸结合域富含亮氨酸重复和吡喃结构域包含蛋白 3（NLRP3）的表达水平，并分析了这些患者的临床数据和生存情况。接下来，研究了 GOLPH3 是否可以通过调节 NLRP3 炎性体来影响肿瘤增殖。结果表明，GOLPH3 可促进 GBC 细胞增殖，并且调节 NLRP3 以及半胱天冬酶-1 P10 的蛋白表达水平。相反，敲低 NLRP3 逆转了 GOLPH3 过表达对 GBC 细胞增殖的影响。发现 GOLPH3 和 NLRP3 的表达在 GBC 组织中上调，且其表达呈正相关。GOLPH3 和 NLRP3 的表达与组织中增殖标志物 Ki-67 的表达相关，并且与 GBC 患者的不良生存、肿瘤分期、分化程度、浸润深度、癌抗原 19-9 和 C 反应蛋白水平相关。总之，这些结果表明，GOLPH3 通过 NLRP3/Caspase-1 通路促进 GBC 细胞增殖。GOLPH3 和 NLRP3 参与了人类 GBC 生长的过程，可能是潜在的治疗靶点。
