Elevated MMP1 Expression in Carcinoma-Associated Fibroblasts of Breast Cancer Contributes to Tumor Progression and Unfavorable Prognosis.

OBJECTIVE: Previous studies have shown that cancer-associated fibroblasts (CAFs) may play a role in tumor growth and development through paracrine action. Several studies reported upregulated matrix metallopeptidase 1 (MMP1) expression in various cancers. The aim is to investigate the role of elevated MMP1 expression in CAFs of breast cancer. METHODS: A total of 203 cases were used for immunohistochemical analysis based on multiple clinical parameters. Tissues for primary cultures of CAFs were collected from 10 breast cancer patients who underwent complete surgical resection of their tumors. MMP1 expression in primary CAFs was detected using reverse transcription-quantitative PCR and western blotting. MMP1-overexpressing CAFs were established via lentiviral transfection, followed by cell functional assays and animal xenograft experiments. RESULTS: MMP1 expression in CAFs of breast cancer was significantly associated with T stage, triple-negative breast cancer status, neoadjuvant chemotherapy status and Ki67 expression. Additionally, MMP1 expression was closely correlated with unfavorable prognosis based on overall survival and disease-free survival analyses. Elevated MMP1 expression in CAFs was verified to promote cell adhesion, invasion, proliferation abilities and attenuate chemosensitivity to Taxotere treatment. CONCLUSION: The results indicated that MMP1 expression in CAFs may participate in the malignant phenotype and unfavorable prognosis of breast cancer.

circCCDC66 promotes thyroid cancer cell proliferation, migratory and invasive abilities and glycolysis through the miR-211-5p/PDK4 axis.

Cancer metastasis is the main cause of death in cancer patients, including patients with thyroid cancer (TC). TC is the most common malignant endocrine tumour. In the recent years, increasing evidence has demonstrated that circular RNAs (circRNAs) serve a significant role in the development of many types of human cancer. However, the function and underlying mechanism of circCCDC66 in TC remain unclear. The present study aimed to explore the role of circCCDC66 in TC. To do so, reverse transcription quantitative PCR was used to detect the expression level of circCCDC66. Cell viability, migratory and invasive abilities, and glucose consumption were evaluated by cell counting kit 8, Transwell and glucose consumption assays, respectively. The association between circCCDC66 or pyruvate dehydrogenase kinase 4 (PDK4) and miR-211-5p was verified by dual-luciferase reporter assay. The results demonstrated that circCCDC66 expression was significantly increased in TC tissues and cell lines. Furthermore, silencing circCCDC66 inhibited TC cell proliferation, migratory and invasive abilities and glycolysis in vitro. Further validation demonstrated that circCCDC66 directly interacted with the microRNA (miR) miR-211-5p. Subsequently, the activity of circCCDC66 was attenuated by miR-211-5p. In addition, the results demonstrated that circCCDC66 may promote papillary thyroid cancer progression by sponging miR-211-5p and increasing expression of PDK4. In conclusion, the present study demonstrated that circCCDC66 could promote TC cell proliferation, migratory and invasive abilities and invasion and glycolysis through the miR-211-5p/PDK4 axis. These findings suggested that targeting circCCDC66 may be considered as a promising therapeutic strategy for TC.

Taxotere-induced WNT16 Expression in Carcinoma-Associated Fibroblasts Might Associate with Progression and Chemoresistance of Breast Cancer.

OBJECTIVE: The objective of this study is to investigate the relationship between WNT16 expression in carcinoma-associated fibroblasts and Taxotere treatments in breast cancer. PROCEDURES: WNT16 expression in primarily cultured carcinoma-associated fibroblasts was detected via Real-Time PCR and Western blot. A total of 106 breast cancer cases were prepared for immunohistochemistry. Multiple assays were performed to examine the function of breast cancer cells (MDA-MB-231) co-cultured with carcinoma-associated fibroblasts when WNT16 was inhibited. RESULTS: Enhanced WNT16 expression was verified in carcinoma-associated fibroblasts after Taxotere treatment (p<0.0001). MDA-MB-231 cells co-cultured with carcinoma-associated fibroblasts displayed decreasing invasion, proliferation abilities, and an increasing sensitivity to Taxotere treatment when WNT16 was inhibited. The WNT16 expression of carcinoma-associated fibroblasts in breast cancer was significantly associated with tumor size (p=0.0164), and chemotherapy treatment (p=0.0015). CONCLUSIONS: The results indicate that Taxotere-induced WNT16 expression in carcinoma-associated fibroblasts might contribute to the progression and chemoresistance of breast cancer.

Fluoxetine Attenuated Anxiety-Like Behaviors in Streptozotocin-Induced Diabetic Mice by Mitigating the Inflammation.

Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.