Downregulation of NCL attenuates tumor formation and growth in HeLa cells by targeting the PI3K/AKT pathway

Cancer Medicine

Ruowang Pan¹  Dadao Huang¹  Enyong Zhang¹  Penghong Hu¹  Ping Ren²  Peizhen Li²  Zhouhao Tang²  Jun Ying²  Yang Lou²  Dong Li²  Jiayin Zhu²  Qiyu Bao² 

[1] No. 906 Hospital of Joint Logistic Support Force of PLA Wenzhou China;School of Laboratory Medicine and Life Science/Institute of Biomedical Informatics Wenzhou Medical University Wenzhou China;

关键词: apoptosis;    HeLa cells;    molecular mechanism;    nucleolin;    PI3K/AKT pathway;    RNA‐Seq;   

DOI  :  10.1002/cam4.4569

来源: DOAJ

【 摘 要 】

Abstract Background Nucleolin (NCL, C23) is a multifunctional phosphoprotein that plays a vital role in modulating the survival, proliferationand apoptosis of cancer cells. However, the effects of NCL on cervical cancer and the underlying mechanisms behind this are poorly understood. Methods Lentiviral transfection technology was used to construct NCL knockdown cell lines. MTT, colony formation assays, and tumorigenic assays in vivo were performed to observe cell proliferation. HOECHST 33342 staining, flow cytometry, and caspase activity assay were used to test cell apoptosis. RNA‐Seq, Western blotting, and RT‐PCR were conducted to investigate the specific molecular mechanism. Results NCL knockdown inhibited cell proliferation and promoted apoptosis both in vivo and in vitro. Mechanistic studies revealed that NCL knockdown inhibited the PI3K/AKT pathway by upregulating FGF, ITGA, TNXB, VEGF, Caspase 3, and Bax, as well as by downregulating AKT, GNB4, CDK6, IL6R, LAMA, PDGFD, PPP2RSA and BCL‐2. In addition, the expression levels of apoptosis‐related genes after using a PI3K inhibitor LY294002 were consistent with shRNA studies, while treatment with a 740Y‐P agonist showed the opposite effect. Conclusions Our findings indicate that downregulation of NCL may be a novel treatment strategy forcervical cancer.

【 授权许可】

Unknown