Background Centromere Protein F (CENPF) associates with the centromere–kinetochore complex and influences cell proliferation and metastasis in several cancers. The role of CENPF in breast cancer (BC) bone metastasis remains unclear. Methods Using the ONCOMINE database, we compared the expression of CENPF in breast cancer and normal tissues. Findings were confirmed in 60 BC patients through immunohistochemical (IHC) staining. Microarray data from GEO and Kaplan–Meier plots were used analyze the overall survival (OS) and relapse free survival (RFS). Using the GEO databases, we compared the expression of CENPF in primary lesions, lung metastasis lesions and bone metastasis lesions, and validated our findings in BALB/C mouse 4T1 BC models. Based on gene set enrichment analysis (GSEA) and western blot, we predicted the mechanisms by which CENPF regulates BC bone metastasis. Results The ONCOMINE database and immunohistochemical (IHC) showed higher CENPF expression in BC tissue compared to normal tissue. Kaplan–Meier plots also revealed that high CENPF mRNA expression correlated to poor survival and shorter progression-free survival (RFS). From BALB/C mice 4T1 BC models and the GEO database, CENPF was overexpressed in primary lesions, other target organs, and in bone metastasis. Based on gene set enrichment analysis (GSEA) and western blot, we predicted that CENPF regulates the secretion of parathyroid hormone-related peptide (PTHrP) through its ability to activate PI3K–AKT–mTORC1. Conclusion CENPF promotes BC bone metastasis by activating PI3K–AKT–mTORC1 signaling and represents a novel therapeutic target for BC treatment.

The accumulation of tumour-associated macrophages (TAMs) in the hypoxic tumour microenvironment (TME) is associated with malignant progression in cancer. However, the mechanisms by which the hypoxic TME facilitates TAM infiltration are not fully understood. This study showed that high ZEB1 expression in hypoxic cervical cancer cell islets was positively correlated with CD163 + TAM accumulation. ZEB1 in hypoxic cancer cells promoted the migration of TAMs in vitro and altered the expression of multiple chemokines, especially CCL8. Mechanistically, hypoxia-induced ZEB1 activated the transcription of CCL8, which attracted macrophages via the CCR2–NF-κB pathway. Furthermore, ZEB1 and CCL8 were independent prognostic factors in cervical cancer patients based on The Cancer Genome Atlas (TCGA) data analysis. In conclusion, hypoxia-induced ZEB1 exerts unexpected functions in cancer progression by fostering a prometastatic environment through increased CCL8 secretion and TAM recruitment; thus, ZEB1 may serve as a candidate biomarker of tumour progression and provide a potential target for disrupting hypoxia-mediated TME remodelling.

Background/aims Radioresistance remains a significant obstacle in the therapy of cervical cancer, and the mechanism of it is still unclear. We aimed to investigate the role of specificity protein 1 (Sp1) in radioresistance of cervical cancer. Methods Sp1 was examined immunohistochemically on tissues from 36 human cervical cancer patients. We used RT-qPCR and Western blot to examine the expression of Sp1 in irradiated cervical cancer cell lines SiHa and HeLa. The role of Sp1 in radioresistance of cervical cancer cells was assessed by colony-formation assay and cell cycle analysis. Dual-luciferase reporter assay was performed to detect the downstream of Sp1. Results High Sp1 expression was positively correlated with advanced International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis, and lymphovascular space invasion (LVSI) of cervical cancer. The expression of Sp1 was dose-dependently increased in irradiated cervical cancer cell lines at both mRNA and protein levels. Colony-formation assay showed that alteration of Sp1 expression affected the survival of cervical cancer cells with radiotherapy (RT) treatment. Knockdown of Sp1 significantly strengthened the cellular response to radiation by inducing G2/M arrest in cervical cancer cells. Overexpression of Sp1 significantly decreased G2/M arrest in cervical cancer cells, which was related to upregulation of CDK1 expression. Dual-luciferase reporter assay showed the direct effect of Sp1 on the transcriptional activation of CDK1. Conclusion Sp1 may contribute to radioresistance through inhibiting G2/M phase arrest by targeting CDK1, and be considered as a potential therapeutic target to promote the effect of RT for patients with cervical cancer.

TRIP13 is a member of the large superfamily of the AAA + ATPase proteins and is associated with a variety of activities. Emerging evidence has shown that TRIP13 may serve as an oncogene. However, the function of TRIP13 in breast cancer (BC) has not yet been elucidated. Here, a variety of bioinformatic tools and laboratory experiments were combined to analyse the expression patterns, prognostic value and functional network of TRIP13 in BC. Multiple databases and immunohistochemistry (IHC) indicated a higher TRIP13 expression in BC tissue compared with normal tissue. TRIP13 was highly expressed in lung metastatic lesions compared with primary tumours in a 4T1 cell implantation BALB/c mouse model of BC. Kaplan–Meier plots also revealed that high TRIP13 expression correlated with poor survival in patients with BC. Furthermore, gene set enrichment analysis revealed that TRIP13 was primarily enriched in the signalling pathway of PI3K‐AKT‐mTOR. Suppressing TRIP13 could inhibit the expression of related genes, as well as the proliferation and migration of BC cell. Finally, 10 hub genes with a high score of connectivity were filtered from the protein–protein interaction (PPI) network, including MAD2L1, CDC20, CDC5L, CDK1, CCNA2, BUB1B, RAD51, SPO11, KIF11 and AURKB. Thus, TRIP13 may be a promising prognostic biomarker and an effective therapeutic target for BC.

No abstract