P4HA3 promotes clear cell renal cell carcinoma progression via the PI3K/AKT/GSK3 beta pathway

作者全名："Zhang, Zhechuan; Zhang, Yuanfeng; Zhang, Ronggui"

作者地址："[Zhang, Zhechuan; Zhang, Yuanfeng; Zhang, Ronggui] Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, 74 Linjiang Rd, Chongqing, Peoples R China; [Zhang, Zhechuan] Chongqing Med Univ, Clin Coll 2, Chongqing, Peoples R China; [Zhang, Ronggui] Chongqing Univ, Cent Hosp, Dept Urol, 1 Jiankang Rd, Chongqing, Peoples R China"

通信作者："Zhang, YF; Zhang, RG (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Urol, 74 Linjiang Rd, Chongqing, Peoples R China.; Zhang, RG (通讯作者)，Chongqing Univ, Cent Hosp, Dept Urol, 1 Jiankang Rd, Chongqing, Peoples R China."

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000906368000001

JCR分区：Q3

影响因子：3.4

年份：2023

卷号：40

期号：2

开始页：　

结束页：　

文献类型：Article

关键词：Clear cell renal cell carcinoma; P4HA3; Tumor progression; Therapeutic target; PI3K-AKT pathway

摘要："Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma. P4HA3 is a key enzyme in collagen biosynthesis and has emerged as important molecules in regulation of proliferation, invasion, and metastasis in various tumor types. The role of P4HA3 in the development of ccRCC has remained to be elucidated. Genes expression, prognostic, and enrichment analyses were carried out with bioinformatics analysis. The efficiency of P4HA3 knockdown was confirmed by real-time quantitative PCR and Western blotting. The cellular functions were analyzed by CCK-8, EdU, wound healing, and transwell assays. The levels of related proteins expression were analyzed by Western blotting. P4HA3 was highly expressed in ccRCC compared with normal tissue samples from the TCGA database. Kaplan-Meier curves results showed that the expression level of P4HA3 was significantly negatively correlated with overall survival of patients. P4HA3 expression knockdown inhibited the proliferation, migration, and invasion of ccRCC cells, as demonstrated by in vitro experiments. In addition, GSEA results revealed that P4HA3 may be related to EMT and involved in the PI3K-AKT-GSK3 beta pathway in ccRCC; this was tentatively confirmed through Western blotting. P4HA3 may induce ccRCC progression via the PI3K-AKT-GSK3 beta signaling pathway and could represent a potential therapeutic target."

基金机构：National Natural Science Foundation of China [81801507]; Research Program of Natural Science Foundation in Chongqing [cstc2021jcyj-msxmX0484]; Kuanren Talent Program of the Second Affiliated Hospital of Chongqing Medical University [KY2019Y004]

基金资助正文："This work was supported by National Natural Science Foundation of China (Grant No. 81801507), Research Program of Natural Science Foundation in Chongqing (cstc2021jcyj-msxmX0484), and Kuanren Talent Program of the Second Affiliated Hospital of Chongqing Medical University (KY2019Y004)."