Overexpression of HOTAIR (HOX antisense intergenic RNA) is significantly correlated with tumor progression and poor prognosis in human ovarian cancer. However, the underlying mechanisms are largely unknown. In the present study, we investigated the roles of HOTAIR in the initiation and chemoresistance of ovarian cancer. As our data show, HOTAIR overexpression promoted cell cycle progression (and thus cell proliferation) by activating the wnt/β-catenin signaling pathway. Likewise, knockdown of HOTAIR suppressed cell proliferation and arrested cell cycle at G1 phase via inhibition of wnt/β-catenin signaling. Moreover, the results of primary culture demonstrated that elevated HOTAIR expression correlated positively with chemoresistance in ovarian cancer. In vitro and in vivo, HOTAIR induced cellular resistance to cisplatin by activating the wnt/β-catenin pathway, which could be reversed by pre-treatment with the wnt/β-catenin inhibitor, XAV939. In conclusion, HOTAIR promotes the initiation and chemoresistance of ovarian cancer by activating wnt/β-catenin signaling, suggesting that HOTAIR might be a potent therapeutic target for ovarian cancer treatment.
Glycolysis is a typical conduit for energy metabolism in pancreatic cancer (PC) due to the hypoxic microenviroment. Lactate dehydrogenase A (LDHA) catalyzes the conversion of pyruvate to lactate and is considered to be a key checkpoint of anaerobic glycolysis. The aim of the present study was to explore the mechanism of interactions between hypoxia, HIF-1/2α and LDHA, and the function of LDHA on PC cells by analyzing 244 PC and paratumor specimens. It was found that LDHA was over-expressed and related to tumor stages. The result of in vitro study demonstrated that hypoxia induced LDHA expression. To explore the relationship between HIF and LDHA, chromatin immunoprecipitation assay and luciferase assay were performed. The result showed that HIF-1/2α bound to LDHA at 89bp under the hypoxic condition. Furthermore, knockdown of endogenous HIF-1α and HIF-2α decreased the LDHA expression even in the hypoxic condition, which was accompanied with a significant decrease in lactate production and glucose utilization (p < 0.01). Immunofluorescence in the 244 specimens showed that HIF-1/2α was over-expressed and associated with LDHA over-expression (p < 0.0001). Forced expression of LDHA promoted the growth and migration of PC cells, while knocking down the expression of LDHA inhibited the cell growth and migration markedly. In summary, the present study proved that HIF1/2α could activate LDHA expression in human PC cells, and high expression of LDHA promoted the growth and migration of PC cells.
Saccadic impairment in Alzheimer's disease (AD) was found in horizontal saccades. The present study extends investigation to vertical saccades in a large number of subjects, including AD and amnestic mild cognitive impairment (aMCI). We examined both horizontal and vertical saccades in 30 healthy elderly, 18 aMCI, and 25 AD. Two tasks were used: gap (fixation target extinguishes prior to target onset) and overlap (fixation stays on after target onset). Eye movements were recorded with the Eyeseecam system. (1) Robust gap effect (shorter latencies in gap than in overlap) exists for AD and aMCI patients as for healthy elderly; (2) abnormal long latency of saccades in gap and overlap tasks for AD relative to healthy elderly and aMCI patients; (3) longer latency for aMCI patients than for healthy elderly for the overlap task; (4) significant correlation between scores of Mini-Mental State Examination (MMSE) and latencies of saccades considering the AD group only; (5) higher coefficient of variation in latency for AD patients than for healthy elderly and for aMCI patients; (6) variability of accuracy and speed is abnormally higher in AD patients than in aMCI and healthy elderly. Abnormalities of latency and latency-accuracy-speed variability reflect deficits of cerebral areas involved in the triggering and execution of saccades; latency of saccades can be used as follow-up test for aMCI and AD patients with its significant correlation with the changes of MMSE scores.
Objective: To investigate the correlation between cerebral small vessel disease (CSVD) burden and motor performance of lower and upper extremities in community-dwelling populations.Methods: We performed a cross-sectional analysis on 770 participants enrolled in the Shunyi study, which is a population-based cohort study. CSVD burden, including white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMBs), perivascular spaces (PVS), and brain atrophy were measured using 3T magnetic resonance imaging. All participants underwent quantitative motor assessment of lower and upper extremities, which included 3-m walking speed, 5-repeat chair-stand time, 10-repeat pronation–supination time, and 10-repeat finger-tapping time. Data on demographic characteristics, vascular risk factors, and cognitive functions were collected. General linear model analysis was performed to identify potential correlations between motor performance measures and imaging markers of CSVD after controlling for confounding factors.Results: For motor performance of the lower extremities, WMH was negatively associated with gait speed (standardized β = -0.092, p = 0.022) and positively associated with chair-stand time (standardized β = 0.153, p < 0.0001, surviving FDR correction). For motor performance of the upper extremities, pronation–supination time was positively associated with WMH (standardized β = 0.155, p < 0.0001, surviving FDR correction) and negatively with brain parenchymal fraction (BPF; standardized β = -0.125, p = 0.011, surviving FDR correction). Only BPF was found to be negatively associated with finger-tapping time (standardized β = -0.123, p = 0.012). However, lacunes, CMBs, or PVS were not found to be associated with motor performance of lower or upper extremities in multivariable analysis.Conclusion: Our findings suggest that cerebral microstructural changes related to CSVD may affect motor performance of both lower and upper extremities. WMH and brain atrophy are most strongly associated with motor function deterioration in community-dwelling populations.
Edited by Tamas DalmayKeywords: miR-374a SRC kinase signaling inhibitor 1 Gastric cancer a b s t r a c t MicroRNAs (miRNAs) play a prominent role in gastric cancer (GC) initiation and progression. In this study, we found that miR-374a expression was up-regulated in human GC cell lines and tissues. Inhibition of miR-374a suppressed GC cell proliferation, migration and invasion in vitro and slowed tumor growth in vivo. SRC kinase signaling inhibitor 1 (SRCIN1) was identified as a direct target of miR-374a. Silencing of SRCIN1 significantly enhanced cell proliferation, migration and invasion, whereas SRCIN1 reintroduction partially abrogated the oncogenic effects of miR-374a. Taken together, these findings suggest that miR-374a functions as a candidate oncogene in GC by directly targeting SRCIN1. miR-374a may therefore be useful as a promising therapeutic target for malignant GC.
Increasing evidence suggests that miR‑205 is frequently dysregulated in many types of human cancers, suggesting its important roles in the initiation and progression of cancer. However, the functions of miR‑205 in human endometrial endometrioid carcinoma (EEC) are still unknown. In this study, we investigated the expression of miR‑205 in both normal endometrium and EEC tissues using TaqMan PCR. Compared to normal tissues, miR‑205 was significantly upregulated in EEC (P<0.001). After transfection of miR‑205 inhibitors into Ishikawa cells (or transfection of miR‑205 mimics into AN3CA cells), we demonstrated that the cellular proliferation, migration and invasion properties were negatively regulated by miR‑205. Moreover, by combination of microRNA target prediction algorithms and luciferase reporter system, we identified estrogen-related receptor‑γ (ESRRG) as a target of miR‑205. In conclusion, we demonstrated frequent upregulation of miR‑205 in EEC. In gain‑of‑function and loss‑of‑function assays, inhibition of miR‑205 reduced cellular proliferation, migration and invasion; vice versa, increased levels of miR‑205 led to upregulated cellular proliferation, migration and invasion. Nonetheless, we identified the ESRRG gene to be a novel target, which could be helpful to elucidate mechanisms underlying the tumorigenesis of EEC.
This Chinese version of NPI is a reliable and valid tool for measuring neuropsychiatric disturbances in patients with AD.
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