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.

Objective: To investigate the effects of phycoerythrin (PE) on the human ovarian cancer cell line SKOV-3 and its antitumor mechanisms from a transcriptional point of view. Methods: SKOV-3 cells were exposed to different concentrations of phycoerythrin. The efficiency of this treatment was evaluated through cell growth inhibition, changes in cell morphology, apoptosis and intracellular ROS levels. High throughput sequencing (RNA-seq) was performed to screen differentially expressed genes (DEGs), which was verified using RT-PCR and Western blotting. Results: PE showed a significant inhibitory effect on the growth of SKOV-3 cells in a time- and dose-dependent manner. H&E staining, electron microscopy and flow cytometry revealed that PE induced apoptosis in SKOV-3 cells. Transcriptome analysis showed that 2963 genes were differentially expressed between untreated or PE-treated cells. GO and KEGG pathway analyses identified 16 classical pathways that were enriched. We verified 8 DEGs including, JNK, GADD45A, EDEM2, RAD23, UBQLN, CAPN1, XBP1, and OS9. These results were consistent with results from transcriptional sequences. Conclusion: The inhibitory effect of PE on SKOV-3 cells was a result of interaction with multiple pathways and signaling molecules. Among these, the ROS/JNK/Bcl-2 signaling pathway, upregulation of JNK, GADD45A and RAD23 as well as downregulation of XBP1 and OS9 played a critical role in the PE -induced apoptosis in human ovarian cancer cells.