Progranulin (PGRN) is a growth factor that is involved in the progression of multiple tumors. However, the effects and molecular mechanisms by which PGRN induces lung cancer remain unclear. The expression level of PGRN was analyzed by conducting immunohistochemistry of the histological sections of lung tissues from non-small-cell lung carcinoma (NSCLC) patients. The proliferation, apoptosis, migration, and invasion of NSCLC cells were assessed by the MTT assay, Western blot, degree of wound healing, and Transwell assays. A nude mouse xenograft model was used to validate the role of PGRN in vivo. The expression level of PGRN was higher in male patients with lung adenocarcinoma than in those with lung squamous cell carcinoma; by contrast, no difference was observed in female patients. The overexpression of PGRN promoted the proliferation and anti-apoptosis of H520 (derived from lung squamous cell carcinoma) cells, whereas knockdown of PGRN inhibited the proliferation and anti-apoptosis of A549 (derived from lung adenocarcinoma) cells. Copanlisib (targeting PI3K) inhibited the increase in the expression of cell anti-apoptosis marker Bcl-2 induced by rhPGRN protein; the PI3K agonist 740 Y–P partially reversed the decrease in Bcl-2 expression induced by PGRN deficiency in both A549 and H520 cells. PGRN increased the expression of Ki-67, PCNA, and Bcl-2 in vivo. PGRN inhibited cell apoptosis depending on the PI3K/Akt/Bcl-2 signaling axis; PGRN positivity correlated with lung adenocarcinoma. PGRN is a potential biomarker for the treatment and diagnosis of NSCLC, especially in lung adenocarcinoma.

颗粒蛋白前体 (PGRN) 是一种参与多种肿瘤进展的生长因子。然而，PGRN诱导肺癌的作用和分子机制仍不清楚。通过对来自非小细胞肺癌 (NSCLC) 患者的肺组织的组织切片进行免疫组织化学分析 PGRN 的表达水平。通过MTT法、Western印迹法、伤口愈合程度和Transwell法评估NSCLC细胞的增殖、凋亡、迁移和侵袭。使用裸鼠异种移植模型验证 PGRN在体内的作用. PGRN在男性肺腺癌患者中的表达水平高于肺鳞癌患者；相比之下，女性患者没有观察到差异。PGRN的过表达促进了H520（来源于肺鳞状细胞癌）细胞的增殖和抗凋亡，而PGRN的敲低抑制了A549（来源于肺腺癌）细胞的增殖和抗凋亡。Copanlisib（靶向PI3K）抑制rhPGRN蛋白诱导的细胞抗凋亡标志物Bcl-2的表达增加；PI3K 激动剂 740 Y-P 部分逆转了 A549 和 H520 细胞中 PGRN 缺乏诱导的 Bcl-2 表达下降。PGRN 增加体内Ki-67、PCNA 和 Bcl-2 的表达. PGRN 根据 PI3K/Akt/Bcl-2 信号轴抑制细胞凋亡；PGRN 阳性与肺腺癌相关。PGRN 是治疗和诊断非小细胞肺癌，尤其是肺腺癌的潜在生物标志物。