Circ-CSNK1G1 promotes cell proliferation, migration, invasion and glycolysis metabolism during triple-negative breast cancer progression by modulating the miR-28-5p/LDHA pathway.

BACKGROUND: Circular RNAs (circRNAs) play a vital role in cancer progression. However, there are still numerous circRNAs that have not been functionally explored. Our study aimed to disclose the role of circ-CSNK1G1 in triple-negative breast cancer (TNBC). METHODS: The expression of circ-CSNK1G1, miR-28-5p and lactate dehydrogenase A (LDHA) mRNA was measured by quantitative real-time polymerase chain reaction (qPCR), and the expression of LDHA protein was measured by western blot. Cell proliferation was assessed using MTT assay and colony formation assay. Cell apoptosis was monitored using flow cytometry assay. Cell migration and cell invasion were investigated using transwell assay. Glycolysis progression was assessed according to glucose consumption, lactate production and ATP/ADP ratio. Tumor formation assay in nude mice was conducted to verify the role of circ-CSNK1G1 in vivo. The interplays between miR-28-5p and circ-CSNK1G1 or LDHA were confirmed by dual-luciferase reporter assay. RESULTS: Circ-CSNK1G1 was upregulated in TNBC tissues and cells. Circ-CSNK1G1 knockdown suppressed cancer cell proliferation, migration, invasion and glycolysis energy metabolism, promoted cell apoptosis in vitro, and blocked tumor growth in vivo. Mechanism analysis showed that circ-CSNK1G1 positively regulated LDHA expression by suppressing miR-28-5p. Rescue experiments presented that circ-CSNK1G1 played functions by targeting miR-28-5p, and miR-28-5p participated in TNBC progression by degrading LDHA. CONCLUSION: Circ-CSNK1G1 promotes cell proliferation, migration, invasion and glycolysis metabolism during TNBC development by regulating the miR-28-5p/LDHA pathway.

Suppression of angiogenesis and tumor growth in vitro and in vivo using an anti-angiopoietin-2 single-chain antibody.

Hepatocellular carcinomas (HCCs) are tumors with a highly developed vascular architecture. HCC cells require access to blood vessels for growth and metastasis; therefore, the inhibition of angiogenesis represents a potential therapeutic target for HCC that may reduce the mortality and morbidity from HCC. Various attempts to develop an anti-angiogenic therapy have been made in past decades; however, modest results have been achieved in clinical trials and the challenge of HCC treatment remains. Single-chain antibodies (scFv) are characterized by low molecular weight, low immunogenicity, high penetration and a short half-life, and are easy to produce on a large scale by genetic engineering. Accordingly, an scFv against a specific angiogenic regulator, such as angiopoietin (Ang), may be a promising anti-angiogenic therapy for HCC. Our previous study indicated that an imbalanced expression of angiopoietin-2 (Ang-2) vs. angiopoietin-1 (Ang-1) in HCCs contributes to initiation of neovascularization and promotes the angiogenesis and progression of HCCs. Therefore, we suggest that specific Ang-2-targeting interventions may be valuable in the treatment of HCC via remodeling the neovascular network and changing the tumor microenvironment. In this study, a prokaryotic expression vector of Ang-2 was constructed and purified human Ang-2 protein was isolated. An scFv against human Ang-2 (scFv-Ang2) was identified and purified via phage display technology, and the effects of scFv-Ang2 in vitro and in vivo on HCC in nude mice were evaluated. The results show that scFv-Ang2 inhibits vascular endothelial growth factor (VEGF) and Ang-2 induces the proliferation, migration and tubule formation of human umbilical vein endothelial cells (HUVECs) in vitro. In the in vivo assay, statistical indices, including tumor weight and volume, metastases to lungs, CD31 expression and the microvessel density (MVD) count in the scFv-Ang2-treated group of mice were significantly lower than those in the control group (P<0.05). In conclusion, the successfully generated scFv-Ang2 showed significant inhibitory effects on the angiogenesis and tumor growth of human HCC in vitro and in vivo.

Skull base metastases from a malignant solitary fibrous tumor of the liver. A case report and literature review.

Solitary fibrous tumors (SFTs) of the liver are rarely described; only 38 cases have been reported in literature, most of which have shown benign clinical characteristics, and only 3 of these cases exhibited malignant variants. In this study, we present a 24-year-old woman with a 1-month history of a rapidly enlarging abdominal mass and a CT showing an exophytic heterogeneous liver mass with a firm parietal bone mass. The patient underwent a transcatheter arterial chemoembolization (TACE) before operation, and an extended right hepatectomy and craniectomy with a negative margin was performed under general anesthesia. The masses showed histological features of oval spindle cells haphazardly arranged in the classic short-storiform or so-called patternless pattern of solitary fibrous tumors. The tumor cells showed positive immunohistochemical reactions to CD34 and bcl-2. The tumor recurred in the residual liver 2 months after operation, metastatic osteoblastic lesions in the thoracic and lumbar vertebrae were identified 3 months after the operation, and lumbar vertebrae metastasis 7 months after operation paralyzed the patient. The patient underwent percutaneous ethanol injection therapy (PEI) and chemotherapy, but the patient died because of the uncontrolled tumor 16 months after the initial operation. To our knowledge, this is the first case of malignant solitary fibrous liver tumors with skeletal metastasis.