PurposeThe aquaporin (AQP) family consists of a number of small integral membrane proteins that transport water and glycerol. AQPs are critical for trans-epithelial fluid transport. Recent reports demonstrated that AQPs, particularly AQP1 and AQP5, are expressed in high grade tumor cells of a variety of tissue origins, and that AQPs are involved in cell migration and metastasis. Based on this background, we examined whether AQP3, another important member of the AQP family, could facilitate cell migration in human breast cancers.MethodsPotential role of AQP3 was examined using two representative breast cancer cell lines (MDA-MB-231 and Bcap-37). Briefly, AQP3 expression was inhibited with a lentivirus construct that stably expressed shRNA against the AQP3 mRNA. AQP3 expression inhibition was verified with Western blot. Cell migration was examined using a wound scratch assay in the presence of fibroblast growth factor-2 (FGF-2). In additional experiments, AQP3 was inhibited by CuSO4. Fibroblast growth factor receptor (FGFR) kinase inhibitor PD173074, PI3K inhibitor LY294002, and MEK1/2 inhibitor PD98059 were used to dissect the molecular mechanism of FGF-2 induced AQP3 expression.ResultsFGF-2 treatment increased AQP3 expression and induced cell migration in a dose dependent manner. Silencing AQP3 expression by a lentiviral shRNA inhibited FGF-2 induced cell migration. CuSO4, a water transport inhibitor selective for AQP3, also suppressed FGF-2-induced cell migration. The FGFR kinase inhibitor PD173074, significantly inhibited FGF-2-induced AQP3 expression and cell migration. The PI3K inhibitor LY294002 and MEK1/2 inhibitor PD98059 inhibited, but not fully blocked, FGF-2-induced AQP3 expression and cell migration.ConclusionsAQP3 is required for FGF-2-induced cell migration in cultured human breast cancer cells. Our findings also suggest the importance of FGFR-PI3K and FGFR-ERK signaling in FGF-2-induced AQP3 expression. In summary, our findings suggest a novel function of AQP3 in cell migration and metastasis of breast cancers.

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Background Breast cancer is the most common cancer among women worldwide, and approximately 70% of breast cancers are hormone receptor-positive and express estrogen receptor-α (ERα) or/and progesterone receptor. ERα has been identified to promote the growth of primary breast cancer, however, it can also antagonize signaling pathways that lead to epithelial-mesenchymal transition (EMT), including transforming growth factor-β (TGF-β) signaling. miRNA alteration or dysfunction is involved in cancer development and progression. Although miR-1271 has identified as a tumor suppressor in various cancers, the role of miR-1271 in breast cancer is still limited. Methods The effect of miR-1271 on breast cancer progression was investigated both in vitro and in vivo. The EMT-related protein expression levels and localization were analyzed by western blotting and immunofluorescence, respectively. Chromatin immunoprecipitation and dual-luciferase reporter assays were used to validate the regulation of ERα-miR-1271-SNAI2 feedback loop. Results miR-1271 suppresses breast cancer progression and EMT phenotype both in vitro and in vivo by targeting SNAI2. Estrogen reverses TGF-β-induced EMT in a miR-1271 dependent manner. Furthermore, ERα transactivates the miR-1271 expression and is also transcriptionally repressed by SNAI2. Conclusions Our data uncover the ERα-miR-1271-SNAI2 feedback loop and provide a mechanism to explain the TGF-β network in breast cancer progression. Electronic supplementary material The online version of this article (10.1186/s13046-019-1112-4) contains supplementary material, which is available to authorized users.

Background: Acupoint catgut embedding therapy characterized by acupoint, needle and catgut are superior to traditional acupuncture, due to exerting more comprehensive therapeutic efficacy. However, it is still deficient in clinical evidence for polyglycolic acid sutures, a novel biodegradable material instead of catgut, embedded for the treatment of simple obesity. In our study, we investigate the efficacy and related mechanism of polyglycolic acid sutures embedded in abdominal acupoints on simple obese persons by a randomized control trial. Methods: A total of 51 eligible participators were randomly allocated to a polyglycolic acid sutures embedding therapy (PASET) group (n = 28) or control group (n = 23). Participators in PASET group received polyglycolic acid sutures alternatively embedded in abdominal I group and II group acupoints in odd and even number therapeutic courses, and participators in control group were required to perform lifestyle modification. The duration of the study was 10 weeks. Results: It suggested that PASET significantly reduced weight, body mass index, hip circumference, waist circumference, waist/hip ratio, waist-to-height ratio and thickness of abdominal subcutaneous fat tissue compared with those before treatment (p < 0.01), but lifestyle modification only illustrated downward trend of weight (p < 0.05). Moreover, PASET group also improved the evaluated scores in aspects of physical function, self-esteem, public distress and sexual life, as well as decreased blood pressure, glycemia, low density lipoprotein, uric acid and the levels of tumor necrosis factor-alpha, interleukin-1β, and increased high density lipoprotein in comparison with those before treatment (p < 0.05), whose efficacies are superior to control group. Additionally, our results also indicate PASET is relative safe and its pain and discomfort can be tolerable. Conclusions: PASET distinctly ameliorates anthropometric data and quality of life in obese population, which associates with improvements of metabolic profile and inflammatory response. Based on the advantageous actions, we think PASET is an effective therapeutic approach to simple obesity treatment.