Autoimmunity

LncRNA SNHG5 promotes cervical cancer progression by regulating the miR-132/SOX4 pathway

The long non-coding RNA (lncRNA) small nucleolar RNA host gene 5 (SNHG5) has been verified as a crucial regulator in many types of tumours but not clear in cervical cancer (CC). This study aims to investigate the effect and further mechanisms of lncRNA SNHG5 in CC. The expression of SNHG5 and miR-132, as well as SOX4 (sex-determining region Y-box 4) mRNA expression were determined by quantitative real-time PCR (qRT-PCR). The protein level of SOX4 and epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot. Then, Edu and Transwell assay were performed to assess the proliferation, migration and invasion of CC cells. RNA immunoprecipitation (RIP) and RNA pull-down assay were conducted to explore the relationship between SNHG5 and miR-132. SNHG5 and SOX4 were upregulated, and miR-132 was downregulated in CC tissues and cell lines. SNHG5 was positively correlated with FIGO stage ( SNHG5 promotes SOX4 expression to accelerate CC cell proliferation, migration and invasion through negatively regulating miR-132.

Hypoxic tumour-derived exosomal miR-1225-5p regulates M2 macrophage polarisation via toll-like receptor 2 to promote ovarian cancer progress

Tumor-secreted exosomes are critical for the functional regulation of tumor-associated macrophages (TAMs). This study aimed to explore how exosomes secreted by ovarian carcinoma cells regulate the phenotype and function of macrophages. Hypoxic treatment of A2780 cells was postulated to mimic the tumor microenvironment, and exosomes were co-cultured with TAMs. miR-1225-5p was enriched in hypoxic exosomes and contributed to M2 macrophage polarizationby modulating Toll-like receptor 2 expression (TLR2). Furthermore, hypoxia-treated macrophages promote ovarian cancer cell viability, migration, and invasion via the wnt/β-catenin pathway. This study clarified that exosomal miR-1225-5p promotes macrophage M2-like polarization by targeting TLR2 to promote ovarian cancer, which may via the wnt/β-catenin pathway.

IL-10 + CD19 + regulatory B cells induce CD4 + Foxp3 + regulatory T cells in serum of cervical cancer patients

Increase of regulatory T cells (Tregs) in the tumour microenvironment predicts worse survival of patients with various types of cancer. Recently, B cells play a significant role in the maintenance of Treg cells. However, the relevance of regulatory B cells (Bregs) to tumour immunity in humans remains elusive. Flow cytometry analysis was used to detect the Bregs and Tregs. Double staining results illustrated that the proportion of Bregs and Tregs were prominently higher in cervical cancer than normal tissues. Increase of Bregs and Tregs in cervical cancer microenvironment was associated with poor survival. Furthermore, Bregs cocultured with cervical cancer cell lines increased and induced Tregs. To sum up, the increased expression of Bregs contributes to the differentiation of CD4

Clinical implication and immunological characterisation of the ARF-GEF family member CYTH4 in ovarian cancer

The GTP exchange factors on ADP-ribosylation factor (ARF) mediate the GDP/GTP exchange on ARF, serve as regulators in protein trafficking and membrane dynamics, and play critical roles in various cell processes. However, the relationship between the expression of ARF-GEF family genes and clinical implications in ovarian cancer remains unclear. We performed a systematic investigation on the role of ARF-GEF family genes in ovarian cancer by using Gene Expression Omnibus (GEO), Kaplan-Meier plotter, Gene set enrichment analysis (GSEA), TIMER and TISIDB database. We found that the ARF-GEF family gene CYTH4 exhibited significant expressional upregulation in ovarian cancer compared to normal ovary tissues. The expression of CYTH4 was also higher in metastases from the omentum than in matched primary ovarian tumours. Kaplan-Meier plotter showed that high expression of CYTH4 predicted worse overall survival, progression free survival and post-progression survival of ovarian cancer patients. Notably, from our correlation analysis, CYTH4 expression showed closely association with tumour-infiltrating immune cells. Intriguingly, the expression of CYTH4 was also significantly correlated with a variety of immunomodulators, chemokines and major histocompatibility complex molecules. Overall, our findings provide a valuable source of data about the clinical significance of CYTH4 in ovarian cancer.

Berberine inhibits the development of endometrial cancer through circ_ZNF608/miR-377-3p/COX2 axis

Endometrial carcinoma (EC) is a common malignant tumour in women. Berberin (BBR) is an alkaloid with anti-tumour activity, and circular RNA (circRNAs) has been extensively studied in cancers. However, whether BBR regulates the development of EC by regulating circular RNA zinc finger protein 608 (ZNF608) is unknown. Different concentrations of BBR were used to treat endometrial cancer cells. A quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess the expression of circ_ZNF608, microRNA-377-3p (miR-377-3p) and cyclooxygenase 2 (COX2). The expression of COX2 protein was detected by western blot. The effect of circ_ZNF608 in BBR-treated EC cells was verified by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) assay, colony formation assay, transwell, and flow cytometry. The effect of BBR and circ_ZNF608 on tumour growth was evaluated by xenograft tumour model Berberine can inhibit the proliferation and metastasis of EC cells and promote apoptosis, which is related to the concentration. Circ_ZNF608 and COX2 were abnormally increased, while the levels of miR-377-3p were reversed in EC tissues and cells. Overexpression of circ_ZNF608 can restore the inhibitory effect of BBR on EC cells. In addition, circ_ZNF608 restored the inhibitory effect of BBR on EC cells by inhibiting the expression of miR-377-3p. Similarly, MiR-377-3p/COX2 can regulate the tumour progression of EC under BBR. Finally, BBR can inhibit the growth of endometrial carcinoma BBR was found to inhibit EC