Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

The present study assessed the effect of the lipid metabolism, fat mass and the obesity-associated gene (FTO), on energy metabolism of breast cancer cells. The human breast cancer cell lines, MCF-7 and MDA-MB-231, and HCC1937 human breast cells were studied. Real-time PCR was used to measure the levels of FTO mRNA from breast cancer cells and normal breast cells. MDA-MB-231 cells were transfected with miFTO inhibitor or inhibitor control, and cells were assessed for levels of lactic acid, ATP, pyruvate kinase activity, and hexokinase activity assay using specific kits. Western blot analysis was used to measure the levels of phosphatidylinositol 3-kinase (PI3K), p-PI3K, protein kinase B (Akt) and p-Akt in transfected breast cancer cells. The expression of FTO was significantly increased in MCF-7 and MDA-MB-231 cells compared with HCC1937 cells (P<0.01). The lactic acid content of breast cancer cells transfected with the miFTO inhibitor was significantly lower compared with cells transfected with the miFTO inhibitor control and nontransfected cells (P<0.05). The ATP content of breast cancer cells transfected with the miFTO inhibitor was significantly lower compared with the control group and inhibitor control group (P<0.05). The pyruvate kinase activity and hexokinase activity of breast cancer cells transfected with the miFTO inhibitor were significantly lower compared with the control group and inhibitor control group (P<0.01). Western blot analysis showed that after breast cancer cells were transfected with the miFTO inhibitor, the levels of PI3K, p-PI3K, Akt and p-Akt were significantly lower than in the control group and inhibitor control group. In conclusion, the FTO gene is overexpressed in breast cancer cells. Overexpression of the FTO gene can promote breast cancer cell glycolysis and the mechanism is related to the PI3K/AKT signaling pathway.

No abstract

Evidence indicates that the largest volume of hospital readmissions occurs among patients with preexisting chronic conditions. Identifying these patients can improve the way hospital care is delivered and prioritize the allocation of interventions. In this retrospective study, we identify factors associated with readmission within 30 days based on claims and administrative data of nine hospitals from 2005 to 2012. We present a data inclusion and exclusion criteria to identify potentially preventable readmissions. Multivariate logistic regression models and a Cox proportional hazards extension are used to estimate the readmission risk for 4 chronic conditions (congestive heart failure [CHF], chronic obstructive pulmonary disease [COPD], acute myocardial infarction, and type 2 diabetes) and pneumonia, known to be related to high readmission rates. Accumulated number of admissions and discharge disposition were identified to be significant factors across most disease groups. Larger odds of readmission were associated with higher severity index for CHF and COPD patients. Different chronic conditions are associated with different patient and case severity factors, suggesting that further studies in readmission should consider studying conditions separately.

Background Although obesity is a well-known risk factor for hyperuricemia, it remains unclear whether obese subjects with metabolically healthy status have a decreased the risk of hyperuricemia and whether sex modifies the association of metabolically healthy obesity (MHO) with hyperuricemia risk. We aimed to investigate the sex-specific association between MHO and other obesity phenotypes and hyperuricemia, and to use Bayesian networks to determine and visualize the interactions among hyperuricemia and its related factors. Methods This study was conducted using data from the China Health and Nutrition Survey 2009. Hyperuricemia was defined as serum uric acid ≥ 420 μmol/L in men and ≥ 360 μmol/L in women according to the guidelines. Body mass index (BMI) was used to define normal weight, overweight, and obese status in subjects, and metabolic health state was defined by the Adult Treatment Panel (ATP)-III and Visceral Adiposity Index (VAI) criteria, respectively. Subjects were categorized into six phenotypes according to their metabolic health and BMI level status. Results Of the 7,364 Chinese adult individuals included, the prevalence of hyperuricemia among MHO women was only 8.5% (95% CI 4.8 to 14.3%), but increased to 30.7% among MUO women, whereas the highest prevalence among men was found in the MUOW phenotype (39.4%, 95% CI 35.4 to 43.6%), compared to 15.4% for male subjects with MHO. After adjusting for confounders, the MHO phenotype was significantly associated with an increased risk of hyperuricemia compared with their MHNW counterparts in women (OR: 1.95, 95% CI: 1.02–3.74) whereas a significant association was not found in men (OR: 1.46, 95% CI: 0.8–2.68). A complex network structure was established by BNs and then used to find connections between hyperuricemia and its related factors, as well as their interrelationships. By using BN reasoning, the probability of having hyperuricemia was 0.076 among MHO men, while it reached 0.124 in MHO women. Conclusions In conclusion, our results demonstrated that the MHO phenotype was significantly associated with the risk of hyperuricemia only in women, not in men. This sex-specific differences in the association may suggest a favorable condition of MHO for Chinese men with respect to hyperuricemia risk, meanwhile more attention should be paid to the increased risk of hyperuricemia among MHO women.