PGRN exacerbates the progression of non-small cell lung cancer via PI3K/AKT/ Bcl-2 antiapoptotic signaling

作者全名："Chen, Sicheng; Bie, Mengjun; Wang, Xiaowen; Fan, Mengtian; Chen, Bin; Shi, Qiong; Jiang, Yingjiu"

作者地址："[Chen, Sicheng; Bie, Mengjun; Wang, Xiaowen; Jiang, Yingjiu] Chongqing Med Univ, Dept Cardiothorac Surg, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Fan, Mengtian; Chen, Bin; Shi, Qiong] Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med, Chongqing 400016, Peoples R China; [Jiang, Yingjiu] Chongqing Med Univ, Dept Cardiothorac Surg, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Jiang, YJ (通讯作者)，Chongqing Med Univ, Dept Cardiothorac Surg, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：GENES & DISEASES

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000870272400001

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：9

期号：6

开始页：1650

结束页：1661

文献类型：Article

关键词：Bcl-2; Cell apoptosis; NSCLC; PGRN; PI3K; Akt

摘要："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 immunohistochem-istry of the histological sections of lung tissues from non-small-cell lung carcinoma (NSCLC) pa-tients. 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 in-crease 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 defi-ciency 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 treat-ment and diagnosis of NSCLC, especially in lung adenocarcinoma."

基金机构：Chongqing Technology Innovation and application development special fund; National Natural ScienceFoundation of China [cstc2019jscx-msxmX0095]; [NSFC 81672103]

基金资助正文："This research was supported by Chongqing Technology Innovation and application development special fund (No.cstc2019jscx-msxmX0095) and National Natural ScienceFoundation of China (No. NSFC 81672103). The authors are responsible for the results and opinions provided by this research, and the sponsor is not responsible for the content published."